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A liquid chromatography electrospray ionization tandem mass spectrometry method with amoxicillin-d 4 as the stable isotope-labeled internal standard for simultaneous quick detection of amoxicillin and clavulanic acid in human plasma was developed and validated. Chromatographic separations were performed on a Hedera ODS-2 column (2.1 × 150 mm, 5 μm). The mobile phases for gradient elution were aqueous solution containing 0.2% acetic acid (AA) (mobile phase A) together with organic phase solution (acetonitrile and methanol mixed solution, mobile phase B). Mass spectrometry was performed using negative electrospray ionization in multiple reaction monitoring mode. The target fragment ion pairs of amoxicillin, clavulanic acid and amoxicillin-d 4 were m/z 364.1 → 223.1, 198.1 → 135.9 and 368.1 → 227.1, respectively. The linear ranges of this method were 40-5,000 ng/ml for amoxicillin and 30-2,500 ng/ml for clavulanic acid, with coefficient of determination > 0.9900. This method validation included selectivity, standard curve, lower limit of quantitation, accuracy, precision, recovery, matrix effect (hemolytic matrix and hyperlipidemic matrix), carryover, stability, dilution reliability and incurred sample reanalysis study. A successful application of this method was realized in a pharmacokinetic study after administration of amoxicillin-clavulanic acid potassium granules., (© 2024 John Wiley & Sons, Ltd.)

The application of advances in personalized medicine requires the support of in vitro diagnostic techniques aimed at the accurate, fast, sensitive, and precise determination of selected biomarkers. Herein, a novel optical centrifugal microfluidic device is developed for clinical analysis and point-of-care diagnostics. Based on compact disc technology, the integrated biophotonic system enables multiple immunoassays in miniaturized mode. The disposable microfluidic discs are made in cyclic olefin copolymer (COP), containing arrays of immobilized probes. In the developed approach, up to six patient samples can each be tested simultaneously. A portable instrument (<2 kg) controls the assay and the high-sensitive reproducible optical detection in transmission mode. Also, the instrument incorporates specific functionalities for personalized telemedicine. The device (analytical method, disc platform, reader, and software) has been validated to diagnose IgE-mediated drug allergies, such as amoxicillin and penicillin G. The total and specific IgE to β-lactam antibiotics were determined in human serum from patients (25 μL). The excellent analytical performances (detection limit 0.24 ng/mL, standard deviation 7-20 %) demonstrated that the developed system could have the potential for a broader impact beyond the allergy field, as it applies to other IVD tests., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:A. Maquieira reports financial support was provided by H2020 program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24 h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: WHO recommends simplified antibiotics for young infants with sepsis in countries where hospitalisation is not feasible. Amoxicillin provides safe, Gram-positive coverage. This study was done to determine pharmacokinetics, drug disposition and interpopulation variability of oral amoxicillin in this demographic., Methods: Young infants with signs of sepsis enrolled in an oral amoxicillin/intramuscular gentamicin treatment arm of a sepsis trial in Karachi, Pakistan, were studied. Limited pharmacokinetic (PK) sampling was performed at 0, 2-3 and 6-8 hours following an index dose of oral amoxicillin. Plasma concentrations were determined by high-performance liquid chromatography/mass spectrometry. Values of ≥2 mg/L were considered as the effect threshold, given the regional minimal inhibitory concentration (MIC) of resistant Streptococcus pneumoniae. RESULTS: Amoxicillin concentrations were determined in 129 samples from 60 young infants. Six of 44 infants had positive blood cultures with predominant Gram-positive organisms. Forty-four infants contributing blood at ≥2 of 3 specified timepoints were included in the analysis. Mean amoxicillin levels at 2-3 hours (11.6±9.5 mg/L, n=44) and 6-8 hours (16.4±9.3 mg/L, n=20) following the index dose exceeded the MIC for amoxicillin (2.0 mg/L) against resistant S. pneumoniae strains. Of 20 infants with three serum levels, 7 showed a classic dose-exposure profile and 13 showed increasing concentrations with time, implying delayed absorption or excretion., Conclusion: Amoxicillin concentrations in sera of young infants following oral administration at 75-100 mg/kg/day daily divided doses exceeds the susceptibility breakpoint for >50% of a 12-hour dosing interval.Oral amoxicillin may hold potential as a safe replacement of parenteral ampicillin in newborn sepsis regimens, including aminoglycosides, where hospitalisation is not feasible., Trial Registration Number: NCT01027429., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of the present study was to elucidate the pharmacokinetic profiles of amoxicillin trihydrate (AMX) in Siamese freshwater crocodiles (Crocodylus siamensis). Crocodiles were administered a single intramuscular injection of AMX, at a dose of either 5 or 10 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 120 hr. The plasma concentrations of AMX were measured using a validated liquid chromatography tandem-mass spectrometry method. AMX plasma concentrations were quantifiable for up to 72 hr (5 mg/kg b.w.) and 96 hr (10 mg/kg b.w.). The elimination half-life (t 1/2λ z ) of AMX following dosing at 5 mg/kg b.w. (8.72 ± 0.61 hr) was almost identical to that following administration at 10 mg/kg b.w (8.98 ± 1.13 hr). The maximum concentration and area under the curve from zero to the last values of AMX increased in a dose-dependent fashion. The average binding percentage of AMX to plasma protein was 21.24%. Based on the pharmacokinetic data, susceptibility break point, and the surrogate PK-PD index (T > MIC, 0.25 μg/ml), intramuscular administration of AMX at dose of 5 mg/kg b.w. every 4 days might be appropriate for the treatment of susceptible bacterial infections in freshwater crocodiles., (© 2020 John Wiley & Sons Ltd.)

Amoxicillin was administered as a single subcutaneous injection at 12.5 mg/kg to four koalas and changes in amoxicillin plasma concentrations over 24 hr were quantified. Amoxicillin had a relatively low average ± SD maximum plasma concentration (C max ) of 1.72 ± 0.47 µg/ml; at an average ± SD time to reach C max (T max ) of 2.25 ± 1.26 hr, and an elimination half-life of 4.38 ± 2.40 hr. The pharmacokinetic profile indicated relatively poor subcutaneous absorption. A metabolite was also identified, likely associated with glucuronic acid conjugation. Bacterial growth inhibition assays demonstrated that all plasma samples other than t = 0 hr, inhibited the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 to some extent. Calculated pharmacokinetic indices were used to predict whether this dose could attain a plasma concentration to inhibit some susceptible Gram-negative and Gram-positive pathogens. It was predicted that a twice daily dose of 12.5 mg/kg would be efficacious to inhibit susceptible bacteria with an amoxicillin minimum inhibitory concentration (MIC) ≤ 0.75 µg/ml such as susceptible Bordetella bronchiseptica, E. coli, Staphylococcus spp. and Streptococcus spp. pathogens., (© 2019 John Wiley & Sons Ltd.)

This study presents the development of an efficient extraction protocol for amoxicillin from plasma with improved solubility and stability using pH control. Solubility and stability of amoxicillin in commonly used extraction solvents were determined using a newly developed stability-indicating high-performance liquid chromatography (HPLC) method. Following this, protein precipitation (PP) mediated sample purification protocol was developed and validated along with the HPLC method for the extracted amoxicillin from rabbit plasma. The protocol was applied in a pharmacokinetic study in rabbits. A five-fold increase in solubility and two-fold increase in stability of amoxicillin was found by addition of acetate buffer (0.1 M, pH 5.0) in acetonitrile. PP mediated extraction protocol containing acetate buffer-acetonitrile (1:18 v/v) resulted in an extraction recovery of >80% for all the samples. The HPLC assay following extraction was found linear (R 2    >0.9999) over the range of 0.2-20 µg/mL with a lower limit of quantification of 0.2 µg/mL. The accuracy of the quality control samples was found between 97-115% and the relative standard deviation (RSD) was found to be below 6% for all samples. The samples were stable in the mobile phase (pH 5.0) for 72 h post-extraction. Amoxicillin-spiked plasma samples were found stable for up to three freeze-and-thaw cycles but, nearly 50% samples had degraded following storage for two months at -20 °C. Pharmacokinetic analysis indicated a half-life of amoxicillin of nearly 1 h following intravenous injection in rabbits, which is similar to that in humans. Thus, a simple and repeatable, extraction protocol was developed using pH control for quantification of amoxicillin from plasma based on its physicochemical properties., (Copyright © 2019. Published by Elsevier B.V.)

A rapid and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was developed for quantification of 7 antibiotics in low sample volumes (50 μL): amoxicillin, azithromycin, cefotaxime, ciprofloxacin, meropenem, metronidazole and piperacillin, for both routine monitoring and pharmacokinetic studies. After protein precipitation by acetonitrile, the antibiotics were separated on an Acquity UPLC HSS T3 column (run time, 4 min). The mobile phase consisted of a mixture of (A) ammonium acetate (pH 2.4; 5 mM) and (B) acetonitrile acidified with 0.1% formic acid, delivered at 500 μl/min in a gradient elution mode. Total time run was 2.75 min. Ions were detected in the turbo-ion-spray-positive and multiple-reaction-monitoring modes. The assay was accurate and reproductible for the quantification of the seven antibiotics in serum samples over large concentration ranges., (Copyright © 2019. Published by Elsevier B.V.)

Aims: To evaluate the relative bioavailability of oral amoxicillin (AMX) tablets in comparison to AMX suspension in Roux-en-Y gastric bypass bariatric subjects., Methods: A randomized, double-blind, cross-over study was performed on the bioavailability of oral AMX tablets and suspension in Roux-en-Y gastric bypass subjects operated at least 3 months previously . Doses of 875 mg of the AMX tablet or 800 mg of the AMX suspension were given to all the subjects, allowing a washout of 7 days between the periods. Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6 and 8 hours after drug administration and the AMX levels were quantified by liquid chromatography coupled with triple quadrupole tandem mass spectrometry. The pharmacokinetic parameters were calculated by noncompartmental analysis, normalized to an 875 mg dose and the bioavailability of the AMX from the tablets was compared to that from the suspension formulation., Results: Twenty subjects aged 42.65 ± 7.21 years and with a body mass index of 29.88 ± 4.36 kg/m 2 were enrolled in the study. The maximum AMX plasma concentration of the tablets and the suspension (normalized to 875 mg) were 7.42 ± 2.99 mg/L and 8.73 ± 3.26 mg/L (90% confidence interval of 70.71-99.11), and the total area under the curve from time zero to infinity were 23.10 ± 7.41 mg.h/L and 27.59 ± 8.32 mg.h/L (90% confidence interval of 71.25-97.32), respectively., Conclusion: The tablets presented a lower bioavailability than the suspension formulation and the total absorbed amount of AMX in these subjects was lower in comparison to the standard AMX absorption rates in nonbariatric subjects, regardless of the formulation., (© 2019 The British Pharmacological Society.)

Background: The investigation of food-drug and plant-drug interactions has become increasingly important. In case of antibiotics, it is essential to achieve and maintain a plasma concentration sufficient for the antimicrobial action. Although, on theoretical basis, the interaction of polyphenols and antibiotics may be hypothesized, experimental data are lacking to assess its clinical relevance. The aim of our study was to assess the interaction between one of the most widely used antibiotics, amoxicillin, and green tea, the most frequently consumed drink with high polyphenol content., Methods: The effects of green tea on the plasma level of amoxicillin was studied in an in vivo experiment in rats. The plasma level of amoxicillin was monitored by LC-MS/MS for 240 min after oral administration. The polyphenol content of green tea was determined by the Folin-Ciocalteu method., Results: The peak plasma concentration of amoxicillin significantly decreased upon its co-administration with green tea, although the AUC 0-240 of the antibiotic did not decrease significantly in the group treated with amoxicillin suspended in green tea., Conclusions: Our results suggest a potentially relevant interaction between green tea and amoxicillin, worth being further studied in humans.

To assess pharmacokinetics of amoxicillin (AMX) in mice, limitations such as a small sampling volume and low drug concentrations have to be addressed. Similar challenges are faced in a clinical framework, e.g. for therapeutic drug monitoring in neonates or small-scale in vitro investigations. An assay enabling quantification of small sample volumes but still at very low concentrations covering a broad concentration range is thus needed. A simple, rapid and highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and successfully validated for quantification of AMX in mouse serum according to European Medicines Agency guidelines. Sample preparation enabled the use of only 10 μL of serum, which is 5-fold less than comparable assays and allows to reduce the number of mice used in pharmacokinetic studies. After protein precipitation with 40 μL chilled methanol and dilution of the supernatant with water, the sample was injected into the LC system on a Poroshell 120 Phenyl Hexyl column (2.1 × 100 mm, 2.7 μm). Chromatographic separation was achieved using a gradient method consisting of acetonitrile and ultra-pure water, both with 0.1% (V/V) formic acid. Positive electrospray ionisation in multiple reaction monitoring mode was used for detection and quantification of AMX. Application to murine study samples demonstrated the reliability of the developed method being accurate and precise with a quantification range from 0.01 to 10 μg/mL. The assay is easily transferable due to a simple sample preparation and confirmed stability of AMX under various applied conditions., (Copyright © 2019. Published by Elsevier B.V.)

Treatment of mink kits with pre-weaning diarrhea (PWD) can be time-consuming and expensive for the farmer, and the efficacy of the treatment procedure may be questioned. Evidence-based treatment protocols for application on affected animals at farms with outbreaks of PWD are lacking. In Denmark, the dams are sometimes treated with amoxicillin, however, it is unknown if it is passed on to the mink kits via the milk. The aim of the present study was to investigate if amoxicillin is transferred via the milk to the kits after oral (PO) and intramuscular (IM) treatment, respectively, of the dam. Moreover, we estimated the concentrations of amoxicillin continuously in serum from the kits up to 8 h after administration. The concentration of amoxicillin was not affected by the route of administration (P = .64) and serum reached the highest level after 8 h (34 ng/mL, CI 95%  = [24.3-47.7]). The serum concentrations of amoxicillin in the mink kits achieved within 8 h were judged too low to exert antimicrobial impact on relevant bacterial species., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Bariatric surgery leads to several anatomo-physiological modifications that may affect pharmacokinetic parameters and consequently alter the therapeutic effect of drugs, such as antibiotics. The pharmacokinetics of oral amoxicillin after Roux-en-Y gastric bypass (RYGB) surgery is unknown., Objectives: The objective of this study was to evaluate the impact of bariatric surgery on the pharmacokinetics of amoxicillin., Methods: This study was performed as a randomized, open-label, single-dose clinical trial, with two periods of treatment, in which obese subjects (n = 8) received an amoxicillin 500 mg capsule orally before and 2 months after the RYGB surgery. The amoxicillin plasma concentration was determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS)., Results: After the surgery, the mean weight loss was 17.03 ± 5.51 kg, and mean body mass index (BMI) decreased from 46.21 ± 2.82 to 38.82 ± 3.32 kg/m 2 . The mean amoxicillin area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration (AUC 0-tlast ) increased significantly (3.5-fold); the maximum plasma concentration (C max ) increased 2.8-fold after the bariatric surgery. No correlation was found between amoxicillin absorption, BMI, and weight loss percentage., Conclusion: The alterations observed in the amoxicillin pharmacokinetics suggest that obese subjects included in this trial had a substantially increase in amoxicillin systemic exposure after RYGB surgery. However, despite this increase, its exposure was lower than the values reported for non-obese volunteers., Trial Registration: Identifiers: NCT03588273.

This study was conducted to determine the passage ratio of amoxicillin into milk and its pharmacokinetics in milk and plasma after intramuscular administration. Five healthy dairy cows (Holstein, weighing 450-500 kg, aged 2-4 years) were used in this study. They received single intramuscular amoxicillin at a dose of 14 mg/kg body weight. Blood and milk samples were collected prior to drug administration (0); after 15, 30, 45, 60, and 90 min; and 2, 3, 4, 6, 8, 10, and 12 hr after administration. The plasma and milk concentrations of amoxicillin were determined using high-performance liquid chromatography with ultraviolet detection. The passage ratio of amoxicillin into milk and plasma was determined using both AUC-based calculation and milk and plasma concentrations at sampling times; it was calculated 0.46 and 0.52, respectively. The terminal half-life and mean residence time of amoxicillin were 6.05 and 8.60 hr in plasma and 2.62 and 5.35 hr in milk, respectively. The C max2 levels of amoxicillin in plasma and milk were measured as 1,096 and 457 ng/ml, respectively. It was observed that amoxicillin exhibited a secondary peak in plasma and milk. This study was the first to report on the passage ratio of amoxicillin into milk in lactating cows., (© 2018 John Wiley & Sons Ltd.)

Purpose: Ilaprazole, the latest proton pump inhibitor, can be used with clarithromycin and amoxicillin as a triple therapy regimen for eradicating Helicobacter pylori. The aim of this study was to evaluate pharmacokinetic drug interactions and safety profiles after coadministration of clarithromycin, amoxicillin, and ilaprazole., Methods: A randomised, open-label, one-way crossover, two parallel sequences study was conducted in 32 healthy subjects. In part 1, the subjects received a single dose of ilaprazole 10 mg in period 1 and clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 6 days in period 2. In part 2, the subjects received clarithromycin 500 mg and amoxicillin 1000 mg once in period 1 and ilaprazole 10 mg twice daily for 6 days in period 2. In both sequences, the three drugs were coadministrated once on day 5 in period 2. Pharmacokinetic evaluations of ilaprazole (part 1), and clarithromycin and amoxicillin (part 2) were conducted., Results: Twenty-eight subjects completed the study. For ilaprazole, the peak concentration (C max ) slightly decreased from 479 (ilaprazole alone) to 446 ng/mL (triple therapy) [Geometric least square mean ratio (90% confidence interval), 0.93 (0.70-1.22)]. The area under the concentration-time curve from 0 h to the last measurable concentration (AUC last ) slightly increased from 3301 to 3538 μg·h/mL [1.07 (0.85-1.35)]. For clarithromycin, the C max slightly decreased from 1.87 to 1.72 μg/mL [0.90 (0.70-1.15)], and AUC last slightly increased from 14.6 to 16.5 μg·h/mL [1.09 (0.87-1.37)]. For amoxicillin, the C max slightly decreased from 9.37 to 8.14 μg/mL [0.86 (0.74-1.01)], and AUC last slightly decreased from 27.9 to 26.7 μg·h/mL [0.98 (0.83-1.16)]. These changes in the PK parameters of each drug were not statistically significant., Conclusions: The coadministration of ilaprazole, clarithromycin, and amoxicillin was tolerable and did not cause a significant PK drug interaction. Thus, a triple therapy regimen comprising ilaprazole, clarithromycin, and amoxicillin may be an option for the eradication of H. pylori. Clinicaltrials.gov number: NCT02998437.

Amoxicillin is used in the treatment and prevention of a wide range of diseases in poultry breeding. However, its short half-life and low bioavailability restrict its clinical application in these species. Entrapment of drugs into polymeric nanoparticles (nps) presents a means to improve gastrointestinal absorption and oral bioavailability of drugs. This study was aimed to overcome limitation of amoxicillin use in poultry breeding. Amoxicillin was loaded into sodium alginate-polyvinyl alcohol (NaAlg-PVA) blend nps, and characterization of the prepared nps was performed. For pharmacokinetic study, commercial male broilers were used and comparative pharmacokinetics of free and nanoparticle form of amoxicillin were investigated. Twenty-one broilers were divided into three groups. All groups received 10 mg/kg drug. Blood samples were collected, and drug plasma concentrations were determined by HPLC. The results demonstrated that the particle size, zeta potential, encapsulation efficiency, and loading capacity of the nps were 513.96 ± 19.46 nm, -45.36 ± 1.35 mV, 43.66 ± 3.30, and 12.06 ± 0.83%, respectively. In vitro drug release exhibited a biphasic pattern with an initial burst release of 18% within 2 hr followed by a sustained release over 22 hr. The pharmacokinetic results showed that amoxicillin nps have higher bioavailability and longer plasma half-life (p < .01) than free amoxicillin. These results indicate that amoxicillin nano formulation is suitable for oral administration in broilers., (© 2018 John Wiley & Sons Ltd.)

A method was developed for the determination of amoxicillin and metronidazole in human serum. The procedure used was hydrophilic interaction chromatography (HILIC) followed by mass spectrometric (MS) detection. Chromatographic separation was achieved on a ZIC-HILIC column and the mobile phase consisted of a mixture of 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile. The method was validated with regard to selectivity, accuracy, precision, calibration, lower limit of quantification (LOQ), extraction recovery and matrix effect. The LOQs were 0.0138 and 0.008 μg/ml for amoxicillin and metronidazole respectively, while for quantification purposes linearity was achieved in the range of 0.1 μg/ml to 6.4 μg/ml for both drugs with correlation coefficients >0.9990. The intraday precision (expressed as %RSD) and the accuracy (expressed as the % deviation from the nominal value) was <15% for both antibiotics at all QC levels. Extraction recoveries for both drugs and internal standards were >80%, while a considerable matrix effect (<60%) was observed for amoxicillin. Finally, the method was applied to the determination of amoxicillin and metronidazole concentrations in serum for 20 patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Penicillins are widely used to treat infections in children; however, the evidence is continuing to evolve in defining the optimal dosing. Modern pediatric pharmacokinetic study protocols frequently favor opportunistic, "scavenged" sampling. This study aimed to develop a small-volume single assay for five major penicillins and to assess the influence of sample degradation on inferences made using pharmacokinetic modeling, to investigate the suitability of scavenged sampling strategies. Using a rapid ultrahigh-performance liquid chromatographic-tandem mass spectrometric method, an assay for five penicillins (amoxicillin, ampicillin, benzylpenicillin, piperacillin, and flucloxacillin) in blood plasma was developed and validated. Penicillin stabilities were evaluated under different conditions. Using these data, the impact of drug degradation on inferences made during pharmacokinetic modeling was evaluated. All evaluated penicillins indicated good stability at room temperature (23 ± 2°C) over 1 h, remaining in the range of 98 to 103% of the original concentration. More-rapid analyte degradation had already occurred after 4 h, with stability ranging from 68% to 99%. Stability over longer periods declined: degradation of up to 60% was observed with delayed sample processing of up to 24 h. Modeling showed that analyte degradation can lead to a 30% and 28% bias in clearance and volume of distribution, respectively, and falsely show nonlinearity in clearance. Five common penicillins can now be measured in a single low-volume blood sample. Beta-lactam chemical instability in plasma can cause misleading pharmacokinetic modeling results, which could impact upon model-based dosing recommendations and the forthcoming era of beta-lactam therapeutic drug monitoring., (Copyright © 2017 American Society for Microbiology.)

Objectives: Amoxicillin is a broad-spectrum beta-lactam antibiotic. Due to its low toxicity, it is commonly used in obstetrics. The objective of this study was to assess amoxicillin concentrations in amniotic fluid, umbilical blood, placenta and maternal serum two hours following oral administration among pregnant women at term and to assess obstetric and non-obstetric factors that might affect amoxicillin's penetration of these tissues., Materials and Methods: A total of 30 full-term pregnant women who qualified for elective Caesarean delivery were included in the study. Amoxicillin at a dose of 500 mg was administered prior to surgery. Amoxicillin levels were determined by diffusion microbial assay., Results: The maternal serum, placental, umbilical blood and amniotic fluid levels of amoxicillin two hours after oral administration were 2.18±1.30 µg/g, 1.00±0.71 µg/g, 1.00±0.73 µg/g, and 0.67±0.59 µg/g, respectively (Table 2). Maternal serum levels of amoxicillin were significantly higher compared to other tissues (p<0.05)., Conclusion: If the target tissues for the use of antibiotic drugs in pregnant patients are the fetus and/or the placenta, the drug should be administered in a higher-than-standard dose than that used to treat infections in non-pregnant patients. Considering that there is a maximum absorbable dose following oral administration, intravenous administration should be considered to prevent failure of antibiotic treatment. A higher dose of amoxicillin should be considered in obese mothers.

Background: Elastomeric pumps can be useful for the administration of antibiotics in the outpatient setting., Objectives: To determine amoxicillin degradation in elastomeric pumps, as well as the effectiveness of amoxicillin treatment administered by elastomeric pumps., Methods: Antibiotic degradation was measured in elastomeric pumps filled with 6 g of amoxicillin in 240 mL of NaCl 0.9% by drawing samples at 12 h intervals when stored in the fridge for 48 h and when worn around the waist for 24 h. Subsequently nine patients were treated with continuous infusions of 8 or 12 g of amoxicillin per day. Plasma amoxicillin concentrations were measured on each visit to the outpatient parenteral antibiotic therapy unit. Clinical outcome was verified 3 months after the end of treatment., Results: Amoxicillin degradation in elastomeric pumps reached 10% after 48 h in the fridge and an additional 30% when worn around the waist for 24 h. Mean plasma drug concentrations achieved with 12 g of amoxicillin per day were 18.5 mg/L (95% CI 13.5-23.5), which is largely above the MIC of amoxicillin-susceptible bacteria. Nine patients treated for various complicated infections were cured and had no unexpected adverse effects., Conclusions: Adequate plasma drug concentrations and favourable clinical outcomes suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps. This treatment modality does not fulfil formal requirements regarding pharmaceutical stability, but the resulting safety impact in patients is probably limited. Therapeutic drug monitoring and a close clinical follow-up are recommended if this route of administration is chosen., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Synthesis, characterization and molecular recognition properties of fluorene based supramolecular cleft 1 is reported. The cleft molecule 1 was prepared in a single-step with good yield (85% yield), by linking Fluorene with 1-ethyl piperazine. The cleft molecule 1 was carefully characterized using various spectroscopic techniques such as NMR and mass spectrometry. The supramolecular interaction of cleft 1 with amoxicillin, 6APA, aspirin, captopril, cefotaxime, ceftriaxone, cefuroxime, diclofenac, penicillin, and cephradine was evaluated by fluorescent spectroscopy. The molecular recognition studies showed that amoxicillin selectively binds with cleft 1 in the presence of other drugs. The analytical method developed for the supramolecular interaction of molecular cleft 1 and amoxicillin was validated at varying pH, concentration and temperature during recognition process. Job's plots indicated that the stochiometry of the interactions between the cleft 1 and the amoxicillin was 1:1., (Copyright © 2017. Published by Elsevier Inc.)

This study aimed to investigate the pharmacokinetic characteristics of amoxicillin (AMX) in Thai swamp buffaloes, Bubalus bubalis, following single intramuscular administration at two dosages of 10 and 20 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 48 h. The plasma concentrations of AMX were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of AMX in the plasma were determined up to 24 h after i.m. administration at both dosages. The C max values of AMX were 3.39 ± 0.18 μg/mL and 6.16 ± 0.18 μg/mL at doses of 10 and 20 mg/kg, respectively. The AUC last values increased in a dose-dependent fashion. The half-life values were 5.56 ± 0.40 h and 4.37 ± 0.23 h at doses of 10 and 20 mg/kg b.w, respectively. Based on the pharmacokinetic data and PK-PD index (T > MIC), i.m. administration of AMX at a dose of 20 mg/kg b.w might be appropriate for the treatment of susceptible Mannheimia haemolytica infection in Thai swamp buffaloes., (© 2016 John Wiley & Sons Ltd.)

Context: The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic inequivalence exist., Aim: This study was planned to ascertain whether bioequivalence of branded and generic amoxicillin capsule is comparable., Settings and Design: An open-label, randomized, single-dose, two-treatment, two-sequence, two-period crossover oral bioequivalence study was conducted in 12 healthy, adult human subjects under fasting condition., Materials and Methods: Serum samples, collected at 8 time points, were analyzed by a validated ultraviolet spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the curve (AUC) 0-t , AUC 0-∞ , C max , and T max were determined along with time above minimum inhibitory concentration (MIC)., Statistical Analysis Used: The log-transformed PK parameters (C max , AUC 0-t , AUC 0-∞ ) were analyzed using a Two One-Sided Test ANOVA in SAS for each parameter. T max and MIC were analyzed by Wilcoxon rank-sum test in GraphPad Prism., Results: Geometric mean ratio of C max fell within bioequivalence criteria. The upper and lower confidence limits of both AUC 0-t and AUC 0-∞ geometric mean ratio fell below bioequivalence criteria. Time above MIC of generic preparation was significantly lower than that of branded version., Conclusions: The generic capsule was not bioequivalent to the branded amoxicillin capsule., Competing Interests: There are no conflicts of interest.

Purpose: Amoxicillin is commonly used in oral surgery for antimicrobial prophylaxis against surgical-site infection and bacteremia because of its effect on oral streptococci. The aim of this study was to determine whether amoxicillin reaches the break-point concentrations in saliva and has any effect on the salivary microbiota, colonizing bacteria on mucosal membranes and on the gingival crevice after a single dose of amoxicillin., Material and Methods: Twenty subjects received 2 g of amoxicillin, per os. The facultative and strictly anaerobic microflora, as well as the streptococcal microflora specifically, were followed from baseline and after 1, 4, and 24 hours. Samples were taken for microbial analysis from saliva, the dorsum of the tongue, and the gingival crevice, and were inoculated and cultured. Plasma samples and saliva samples were analyzed for amoxicillin concentrations (free and protein bound) using liquid chromatography and mass-spectrometry., Results: Amoxicillin was detected in concentrations over the break-point (>2 μg/mL) of amoxicillin in plasma after 1 and 4 hours but not after 24 hours. The dose had a significant effect on the streptococci in the gingival crevice., Conclusion: A single dose given as prophylaxis to prevent a surgical-site infection results in a significant reducing effect on the oral streptococcal microflora in the gingival crevice and may have an impact on bacteria spreading into tissues and the bacteremia of streptococci., (© 2015 Wiley Periodicals, Inc.)

A simple and rapid ultra-high-performance liquid chromatography (UHPLC) method using UV detection was developed for the simultaneous determination of eight β-lactam antibiotics in human plasma, including four penicillins, amoxicillin (AMX), cloxacillin (CLX), oxacillin (OXA), and piperacillin (PIP), and four cephalosporins, cefazolin (CFZ), cefepime (FEP), cefotaxime (CTX), and ceftazidime (CAZ). One hundred-microliter samples were spiked with thiopental as an internal standard, and proteins were precipitated by acetonitrile containing 0.1% formic acid. Separation was achieved on a pentafluorophenyl (PFP) column with a mobile phase composed of phosphoric acid (10 mM) and acetonitrile in gradient elution mode at a flow rate of 500 μl/min. Detection was performed at 230 nm for AMX, CLX, OXA, and PIP and 260 nm for CFZ, FEP, CTX, and CAZ. The total analysis time did not exceed 13 min. The method was found to be linear at concentrations ranging from 2 to 100 mg/liter for each compound, and all validation parameters fulfilled international requirements. Between- and within-run accuracy errors ranged from -5.2% to 11.4%, and precision was lower than 14.2%. This simple method requires small-volume samples and can easily be implemented in most clinical laboratories to promote the therapeutic drug monitoring of β-lactam antibiotics. The simultaneous determination of several antibiotics considerably reduces the time to results for clinicians, which may improve treatment efficiency, especially in critically ill patients., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

The purpose of this study was to investigate the pharmacokinetic characteristics of amoxicillin (AMX) trihydrate in male Asian elephants, Elephas maximus, following intramuscular administration at two dosages of 5.5 and 11 mg/kg body weight (b.w.). Blood samples were collected from 0.5 up to 72 h. The concentration of AMX in elephant plasma was measured using liquid chromatography electrospray ionization mass spectrometry. AMX was measurable up to 24 h after administration at two dosages. Peak plasma concentration (Cmax ) was 1.20 ± 0.39 μg/mL after i.m. administration at a dosage of 5.5 mg/kg b.w., whereas it was 3.40 ± 0.63 μg/mL at a dosage of 11 mg/kg b.w. A noncompartment model was developed to describe the disposition of AMX in Asian elephants. Based on the preliminary findings found in this research, the dosage of 5.5 and 11 mg/kg b.w. produced drug plasma concentrations higher than 0.25 mg/mL for 24 h after i.m. administration. Thereafter, i.m. administration with AMX at a dosage of 5.5 mg/kg b.w. appeared a more suitable dose than 11 mg/kg b.w. However, more studies are needed to determine AMX clinical effectiveness in elephants., (© 2015 John Wiley & Sons Ltd.)

Rapid, accurate and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods were developed and validated for the simultaneous quantitation of amoxicillin and clavulanic acid in human plasma and urine samples. Amoxicillin and clavulanic acid in both plasma and urine were extracted using a solid-phase extraction method. The compounds were separated on an Acquity UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm). Ampicillin was used as the internal standard (IS) in plasma, while amoxicillin-d 4 and sulbactam were used as ISs in urine. The lower limit of quantitation was 0.0500 and 0.0250 μg/mL for amoxicillin and clavulanic acid in plasma, and 0.0500 μg/mL for both analytes in urine. The established methods were validated in terms of selectivity, precision, accuracy, linearity, matrix effect, recovery, carryover, interaction, dilution integrity and stability, and successfully applied to a pharmacokinetic study of amoxicillin sodium and clavulanate potassium (10:1) injection in healthy volunteers.

1. The pharmacokinetics (PK) and withdrawal period of amoxicillin sodium in olive flounder and its activity against pathogenic bacteria of olive flounder were investigated. 2. Intramuscular administration (12.5 or 125 mg/kg, n = 160) and HPLC analysis of sera were used. 3. Rapid absorption (Tmax 2.6 and 2.2 h), prolonged action (terminal half-life, 15.52 and 10.42 h; MRT, 18.79 and 14.44 h), and dose-proportional exposure (AUC0-∞, 273.69 and 2755.37 h. μg/ml) were observed after 12.5 and 125 mg/kg doses. 4. The withdrawal period of amoxicillin sodium from muscle plus skin of olive flounder (n =40, water temperature, 23 °C) was 12 d (276 degree days). 5. Amoxicillin sodium had small MICs against Streptococcus iniae (0.008-0.06 μg/ml) and Streptococcus parauberis (0.03-1.0 μg/ml), whereas higher concentrations were required to inhibit Edwardsiella tarda isolates (0.06-16 μg/ml). 6. While large AUC0-24 h/MIC90 and Cmax/MIC90 ratios were obtained for S. iniae and S. parauberis, with drug concentrations in serum greater than MICs for the entire dosing interval (T > MIC90 of 100%), the lower dose (12.5 mg/kg) could not achieve target values of the PK-pharmacodynamic (PD) indices for E. tarda isolates, suggesting the need for higher doses to combat pathogenic bacteria with large MICs.

Studies have shown that administration of the β-lactam antibiotic ceftriaxone (CEF) attenuates ethanol consumption and cocaine seeking behavior as well as prevents ethanol-induced downregulation of glutamate transporter 1 (GLT-1) expression in central reward brain regions. However, it is not known if these effects are compound-specific. Therefore, the present study examined the effects of two other β-lactam antibiotics, amoxicillin (AMOX) and amoxicillin/clavulanate (Augmentin, AUG), on ethanol drinking, as well as GLT-1 and phosphorylated-AKT (pAKT) levels in the nucleus accumbens (Acb) and medial prefrontal cortex (mPFC) of alcohol-preferring (P) rats. P rats were exposed to free-choice of ethanol (15% and 30%) for five weeks and were given five consecutive daily i.p. injections of saline vehicle, 100 mg/kg AMOX or 100mg/kg AUG. Both compounds significantly decreased ethanol intake and significantly increased GLT-1 expression in the Acb. AUG also increased GLT-1 expression in the mPFC. Results for changes in pAKT levels matched those for GLT-1, indicating that β-lactam antibiotic-induced reductions in ethanol intake are negatively associated with increases in GLT-1 and pAKT levels within two critical brains regions mediating drug reward and reinforcement. These findings add to a growing literature that pharmacological increases in GLT-1 expression are associated with decreases in ethanol intake and suggest that one mechanism mediating this effect may be increased phosphorylation of AKT. Thus, GLT-1 and pAKT may serve as molecular targets for the treatment of alcohol and drug abuse/dependence., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The study was aimed at investigating the pharmacokinetics of amoxicillin trihydrate (AMOX) in olive flounder (Paralichthys olivaceus) following oral, intramuscular, and intravenous administration, using high-performance liquid chromatography following. The maximum plasma concentration (Cmax ), following oral administration of 40 and 80 mg/kg body weight (b.w.), AMOX was 1.14 (Tmax , 1.7 h) and 0.76 μg/mL (Tmax , 1.6 h), respectively. Intramuscular administration of 30 and 60 mg/kg of AMOX resulted in Cmax values of 4 and 4.3 μg/mL, respectively, with the corresponding Tmax values of 29 and 38 h. Intravenous administration of 6 mg/kg AMOX resulted in a Cmax of 9 μg/mL 2 h after administration. Following oral administration of 40 and 80 mg/kg AMOX, area under the curve (AUC) values were 52.257 and 41.219 μg/mL·h, respectively. Intramuscular 30 and 60 mg/kg doses resulted in AUC values of 370.274 and 453.655 μg/mL·h, respectively, while the AUC following intravenous administration was 86.274 μg/mL·h. AMOX bioavailability was calculated to be 9% and 3.6% following oral administration of 40 and 80 mg/kg, respectively, and the corresponding values following intramuscular administration were 86% and 53%. In conclusion, this study demonstrated high bioavailability of AMOX following oral administration in olive flounder., (© 2014 John Wiley & Sons Ltd.)

Objective: The aim of this study was to assess the amoxicillin concentration in maternal serum, cord blood, amniotic fluid and the placenta, 2 h following vaginal administration and the factors influencing the drug level., Methods: Twenty-eight full-term pregnant women who qualified for elective cesarean delivery were included in the study. Vaginal suppositories containing 250 mg of amoxicillin were administered 2 h prior to the operation. Amoxicillin levels were determined using the diffusion microbial assay., Results: The amoxicillin level in amniotic fluid was significantly higher in comparison to that of maternal serum, cord blood or the placenta. Maternal age positively and gestational weight gain negatively correlated with the amoxicillin concentration in maternal serum. The maternal serum hemoglobin level and red blood cell count were positively correlated with amoxicillin concentration in the amniotic fluid. Neonatal birth weight was positively correlated with maternal serum and cord blood amoxicillin levels. Hypertensive women had significantly higher amoxicillin concentrations in amniotic fluid, and women with thrombocytopenia presented significantly higher cord blood amoxicillin concentrations., Conclusions: Amoxicillin presented poor concentration in maternal-fetal compartments after vaginal administration, but the factors influencing the drug level in different compartments require further investigation.

During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance. To prevent these effects, we developed an enteric-coated formulated activated-charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours thereafter. The AUC0-96 h of amoxicillin was reduced by more than 70% when it was taken with FAC, but bioequivalent when it was taken with water or DAV132. By contrast, the AUC0-96 h of sulfapyridine was reduced by more than 90% when administered with either FAC or DAV132 in comparison with water. The results show that DAV132 can selectively adsorb drug compounds in the proximal colon, without interfering with drug absorption in the proximal small intestine, thereby constituting a proof of concept that DAV132 actually functions in humans., (© 2014, The American College of Clinical Pharmacology.)

The objectives of this study were to develop a new deproteinization method to extract amoxicillin from human plasma and evaluate the inter-ethnic variation of amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose, randomized, fasting, two-period, two-treatment, two-sequence crossover, open-label bioequivalence study was conducted in 18 healthy Malay adult male volunteers, with one week washout period. The drug concentration in the sample was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean (standard deviation) pharmacokinetic parameter results of Moxilen® were: peak concentration (Cmax ), 6.72 (1.56) µg/mL; area under the concentration-time graph (AUC0-8 ), 17.79 (4.29) µg/mL h; AUC0-∞ , 18.84 (4.62) µg/mL h. Those of YSP Amoxicillin® capsule were: Cmax , 6.69 (1.44) µg/mL; AUC0-8 , 18.69 (3.78) µg/mL h; AUC00-∞ , 19.95 (3.81) µg/mL h. The 90% confidence intervals for the logarithmic transformed Cmax , AUC0-8 and AUC0-∞ of Moxilen® vs YSP Amoxicillin® capsule was between 0.80 and 1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. Both formulations were well tolerated. The results showed significant inter-ethnicity variation in pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay population were slightly lower compared with other populations., (Copyright © 2014 John Wiley & Sons, Ltd.)

Purpose: To compare the pharmacokinetic profiles and to evaluate the bioequivalence of two commercial amoxicillin suspension formulations (500 mg/5 mL AMOXIL®, reference formulation and AMOXI-PED®, test formulation) in healthy Brazilian volunteers., Methods: Under fasting condition, 25 volunteers (13 males and 12 females) were included in this randomized, open-label, two-period crossover (1-week washout interval) bioequivalence study. Blood samples were collected at pre-dose (0 hour) and 0.5, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 12 hours after drug ingestion. Pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0-tlast, and AUC0-∞) were calculated from plasma concentrations for both formulations in each subject., Results: Arithmetic mean values of the pharmacokinetic parameters were: Cmax = 12.004 (± 2.824) μg×mL-1; tmax = 1.118 (± 0.396) h; t1/2 = 1.226 (± 0.179) h; AUC0-tlast = 29.297 (± 6.007) μg×h×mL-1; and AUC0-∞ = 29.299 (± 6.007) μg×h×mL-1 for reference formulation and Cmax = 11.456 (± 2.825) μg×mL-1; tmax = 1.331 (± 0.509) h; t1/2 = 1.141 (± 0.133) h; AUC0-tlast = 28.672 (± 5.778) μg×h×mL-1; and AUC0-∞ = 28.693 (± 5.796) μg×h×mL-1 for test formulation. The confidence intervals (90% CI) for reference and test formulations were, respectively, 90.74 - 100.46% for Cmax and 93.62 - 103.61% for AUC0-t., Conclusion: Based on the results, both formulations of amoxicillin evaluated in this study were considered bioequivalent according to FDA and ANVISA/Brazil criteria.

Sensitive and selective analytical procedures based on high-performance liquid chromatography with mass spectrometric detection were developed for the determination of amoxicillin in human plasma samples. Samples were prepared by applying in-house manufactured molecularly imprinted solid-phase microextraction probes. The detection of target compounds was performed in multiple reaction monitoring mode. The multiple reaction monitoring detection was operated in the positive electrospray ionization mode using the transitions of m/z 366 ([M + H](+) ) → 349 for amoxicillin and m/z 390 ([M + H](+) ) → 372 for gemifloxacin. The method was validated with precision within 15% relative standard deviation and accuracy within 15% relative error. The method was successfully applied to study of the pharmacokinetics of amoxicillin in human plasma after oral administration of amoxicillin., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: To determine pharmacodynamic cutoffs with pharmacokinetic-pharmacodynamic principles and Monte Carlo simulation (MCS) for use of amoxicillin in pigs to set interpretive criteria for antimicrobial susceptibility testing., Sample: 191 plasma disposition curves of amoxicillin obtained from 21 IV, 104 IM, and 66 PO administrations corresponding to 2,098 plasma concentrations., Procedures: A population model of amoxicillin disposition in pigs was developed for PO and IM administration. The MCS method was then used to determine, for various dosage regimens, the proportion of pigs achieving plasma amoxicillin concentrations greater than a selection of possible minimal inhibitory concentrations (MICs) ranging from 0.0625 to 4 mg/L for at least 40% of a 24-hour period., Results: A target attainment rate (TAR) of 90% was never achieved with the breakpoint recommended by the Clinical and Laboratory Standards Institute (0.5 mg/L) when the usual recommended dosage (20 mg/kg/d) was used. Only by dividing the orally administered daily dose into 12-hour administration intervals was a TAR > 90% achieved when the total dose was at least 40 mg/kg for a pathogen having an MIC ≤ 0.0625 mg/L. For the IM route, the TAR of 90% could only be achieved for MICs of 0.0625 and 0.125 mg/L with the use of 15 and 30 mg/kg doses, respectively., Conclusions and Clinical Relevance: Population kinetics and MCS are required to determine robust species-specific interpretive criteria (susceptible, intermediate, and resistant classifications) for antimicrobial susceptibility testing breakpoints (taking into account interanimal variability).

Amoxicillin (AMO) degrades in plasma at room temperature and readily undergoes hydrolysis by the plasma amidase. In this paper, a novel, rapid and sensitive LC-MS/MS method operated in segmental and multiple reaction monitoring has been developed for the simultaneous determination of amoxicillin and ambroxol in human plasma. The degradation of amoxicillin in plasma was well prevented by immediate addition of 20 μL glacial acetic acid to 200 μL aliquot of freshly collected plasma samples before storage at -80°C. The sensitivity of the method was improved with segmental monitoring of the analytes, and lower limits of quantitation of 0.5 ng/mL for ambroxol and 5 ng/mL for amoxicillin were obtained. The sensitivity of our method was five times better than those of the existing methods. Furthermore, the mass response saturation problem with amoxicillin was avoided by diluting the deproteinized plasma samples with water before injection into the LC-MS/MS system. The method was successfully employed in a pharmacokinetic study of the compound amoxicillin and ambroxol hydrochloride tablets., (Copyright © 2012 John Wiley & Sons, Ltd.)

A simple sample preparation method has been developed for the determination of amoxicillin in human plasma by hollow fiber centrifugal ultrafiltration (HF-CF-UF). A 400-μL plasma sample was placed directly into the HF-CF-UF device, which consisited of a slim glass tube and a U-shaped hollow fiber. After centrifugation at 1.25 × 10(3) g for 10 min, the filtrate was withdrawn from the hollow fiber and 20 µL was directly injected into the high-performance liquid chromatography (HPLC) for analysis. The calibration curve was linear over the range of 0.1-20 µg/mL (r = 0.9996) and the limit of detection was as low as 0.025 µg/mL. The average recovery and absolute recovery were 99.9% and 84.5%, respectively. Both the intra-day and inter-day precisions (relative standard deviation) were less than 3.1% for three concentrations (0.25, 2.5 and 10 µg/mL). The sample preparation process was simplified. Only after a single centrifugal ultrafiltration can the filtrate be injected directly into HPLC. The present method is simple, sensitive and accurate. It could be effective for the analysis of biological samples with high protein contents, especially for the biopharmaceutical analysis of drugs that use traditional isolation techniques for sample preparation such as the protein precipitation method.

Sensitive and selective analytical procedures based on high performance liquid chromatography with mass spectrometric detection were developed for the determination of linezolid (LIN) and amoxicillin (AMOX) in human plasma samples. Samples were prepared by applying protein precipitation (PP), solid phase extraction (SPE), and microextraction in packed syringe (MEPS). The analytical separation was carried out using reversed phase liquid chromatography in isocratic mode. All analytes were monitored by mass spectrometry (MS) detection in the product ion mode and the method was validated covering the corresponding therapeutic range of 1-30 μg/mL and 1-50 μg/mL for LIN and AMOX respectively. The assay was linear over AMOX and LIN concentration ranges. The method provided good validation data: accuracy (102.9% (LIN), 100.9% (AMOX)), limit of detection (0.1407 ng/mL (LIN); 0.1341 ng/mL (AMOX); quantification (0.3814 ng/mL (LIN), 0.4249 ng/mL (AMOX)) and acceptable stability within 24h in the auto-sampler. Three different methods were compared as regards precision, accuracy, recovery and matrix effects. The proposed methods offer a fast and simple way to determine selected antibiotic drugs in human plasma that could be applied in pharmacokinetic studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A study of amoxicillin pharmacokinetics was conducted in healthy goats and goats with chronic lead intoxication. The intoxicated goats had increased serum concentrations of liver enzymes (alanine aminotransferase and γ-glutamyl transferase), blood urea nitrogen, and reactivated δ-aminolevulinic acid dehydratase compared to the controls. Following intravenous amoxicillin (10 mg/kg bw) in control and lead-intoxicated goats, elimination half-lives were 4.14 and 1.26 h, respectively. The volumes of distribution based on the terminal phase were 1.19 and 0.38 L/kg, respectively, and those at steady-state were 0.54 and 0.18 L/kg, respectively. After intramuscular (IM) amoxicillin (10 mg/kg bw) in lead-intoxicated goats and control animals, the absorption, distribution, and elimination of the drug were more rapid in lead-intoxicated goats than the controls. Peak serum concentrations of 21.89 and 12.19 μg/mL were achieved at 1 h and 2 h, respectively, in lead-intoxicated and control goats. Amoxicillin bioavailability in the lead-intoxicated goats decreased 20% compared to the controls. After amoxicillin, more of the drug was excreted in the urine from lead-intoxicated goats than the controls. Our results suggested that lead intoxication in goats increases the rate of amoxicillin absorption after IM administration and distribution and elimination. Thus, lead intoxication may impair the therapeutic effectiveness of amoxicillin.

Novel molecularly imprinted polymer (MIP)-coated fibers for solid-phase microextraction (SPME) fibers were prepared by using linezolid as the template molecule. The characteristics and application of these fibers were investigated. The polypyrrole, polythiophene, and poly(3-methylthiophene) coatings were prepared in the electrochemical polymerization way. The molecularly imprinted SPME coatings display a high selectivity toward linezolid. Molecularly imprinted coatings showed a stable and reproducible response without any influence of interferents commonly existing in biological samples. High-performance liquid chromatography with spectroscopic UV and mass spectrometry (MS) detectors were used for the determination of selected antibiotic drugs (linezolid, daptomycin, amoxicillin). The isolation and preconcentration of selected antibiotic drugs from new types of biological samples (acellular and protein-free simulated body fluid) and human plasma samples were performed. The SPME MIP-coated fibers are suitable for the selective extraction of antibiotic drugs in biological samples.

Background & Objectives: Nigella sativa Linn. is extensively used in the Indian diasporas as spice, which may interact with co-administered drugs and affect their intestinal availability. The purpose of this study was to investigate the effect of Nigella on bioavailability of amoxicillin in animal model., Methods: Everted rat intestinal sacs were used for in vitro experiment to study the transfer of amoxicillin across the gut. Amoxicillin (6 mg/ml) was co-infused with 3 and 6 mg of methanol and hexane extract of Nigella seeds separately. The amount of amoxicillin that traversed the gut was followed spectrophotometrically at 273 nm. For in vivo studies Wistar albino rats were used. Amoxicillin (25 mg/kg, po) was co-administered with hexane extract of Nigella seeds (25 mg/kg, po). The amount of amoxicillin in rat plasma was determined by UPLC-MS/MS method., Results: The in vitro studies both with methanol and hexane extracts of Nigella increased the permeation of amoxicillin significantly (P<0.001) as compared to control. Permeation was also found to be significantly higher for the hexane extract (P<0.001) in comparison to methanol extract at the same dose levels. In vivo experiments revealed that Cmax of amoxicillin in rat plasma when administered orally alone and in combination with hexane extract increased correspondingly from 4138.251 ± 156.93 to 5995.045 ± 196.28 ng/ml while as AUC 0→t increased from 8890.40 ± 143.33 to 13483.46 ± 152.45 ng/ml.h., Interpretation & Conclusions: Nigella enhanced amoxicillin availability in both in vivo and in vitro studies. As the increase in bioavailability is attributed, in part, to enhanced diffusivity across intestine, our study indicated that Nigella increased intestinal absorption of amoxicillin.

Systemic bioavailability is usually determined from plasma data. However, when plasma is difficult to access, as in young children, alternative methods would be particularly beneficial. The present study investigates the possibility of calculating systemic bioavailability fraction (F) from skin concentrations measured by two microdialysis (MD) sampling methods: continuous microdialysis and intermittent microdialysis. When the drug concentration in skin is a linear and time-invariant function of plasma concentration, the area under the drug concentration curve in skin is directly proportional to the drug absorbed systemically. To verify this theory, we compared the F estimated from MD concentrations in the skin with that obtained from the plasma data in the same experiment. Two model drugs were selected for the study: amoxicillin and ketoprofen. Drugs were administered to rabbits as intravenous infusion or oral suspension according to a randomized crossover design. F estimated by either MD method was not significantly different from that obtained from the plasma for both drugs tested. However, the skin data exhibited a larger variability. These results confirm that skin MD could be an alternative way to obtain data for the calculation of systemic fraction of drug absorbed., (Copyright © 2011 Wiley-Liss, Inc.)

The aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method.Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin.For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 ml/min, even though doses were adapted for renal impairment. the correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens.Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment.

Beta-lactam antimicrobials, commonly used in both veterinary and human medicine, generally present short biologic half-lives, whereas their activity is enhanced as pathogen exposure is prolonged. These properties necessitate multiple-dose regimens of standard dosage forms, thereby hampering pet owner adherence, frequently resulting in therapeutic failure. This study presents a novel controlled-release gastroretentive oral drug delivery system for beta-lactams with which single-dose administration provides an effective antimicrobial course, optimizing pharmacokinetic (PK)-pharmacodynamic (PD) profiles, minimizing adverse effects and emergence of antimicrobial resistance and facilitating adherence. Our prototype sustained-delivery swelling-tablet (SDST), based on a degradable hydrophilic polymeric matrix, was designed to enable continuous input of these drugs to their absorption sites over several days. Several SDST formulations of the beta-lactam amoxicillin were evaluated in in vitro dissolution studies. Two formulations were selected for further in vivo canine studies, for determination of gastric retention and PK-PD profiling. Prolonged gastric retention times maintaining allowed for maintained effective drug concentrations against many clinically relevant pathogens for more than 48 h for one formulation and more than 5 days for the other. Both SDST formulations offer significant advantages over standard immediate-release therapy in achieving PK-PD goals and enhancing adherence. The prototypical formulations represent a novel platform which may be modified to meet various clinical requirements., (© 2010 Blackwell Publishing Ltd.)

A simple and accurate high-performance liquid chromatography with diode array detection-based (HPLC-DAD) method has been developed and validated for simultaneous determination of amoxicillin and sulbactam in human plasma. Sample preparation was involved in protein precipitation with acetonitrile followed by one-step extraction procedure. Chromatographic separation was achieved on a C18 column with an isocratic mobile phase consisting of water (containing 30 mM potassium dihydrogen phosphate, pH 2.8) and acetonitrile. The detection wavelengths of a diode array detector were set at 210 nm for amoxicillin and sulbactam, and 263 nm for the internal standard (cefadroxil). The method was validated for linearity, accuracy, precision, and stability. The calibration curve was linear from 0.163 to 14.7 μg/mL with correlation coefficient squared of 0.9991 for amoxicillin and 0.250-15.0 μg/mL with correlation coefficient squared of 0.9988 for sulbactam using 500 μL plasma samples. The lower limit of quantification was 0.163 and 0.250 μg/mL for amoxicillin and sulbactam, respectively. The imprecisions of intra- and inter-day validations for amoxicillin and sulbactam were <11% and their accuracies (%) were within the range of 95.4-105.7%. Mean recoveries were 75.9, 72.8, and 70.0% for amoxicillin, sulbactam, and cefadroxil, respectively. The established method was successfully applied to a bioequivalence study of two combination formulations of amoxicillin and sulbactam pivoxil in healthy male volunteers., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)