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Background: Despite rifampicin and ethambutol being widely used to treat patients with tuberculosis, reports of potentially lethal overdoses of these drugs are rare. The toxic effects of rifampicin become apparent at doses of 9–12 g, and become potentially fatal at doses over 14 g. Case presentation: We describe a case of severe rifampicin (18 g) and ethambutol (25 g) poisoning that was successfully managed using hemoperfusion (HP) and hemodiafiltration (HDF) in conjunction with serum blood drug concentration monitoring. A 57-year-old female was rushed to the emergency room of Shenzhen Third People's Hospital (China) 4 hours after she ingested 120 tablets of rifampicin (18 g) and 100 tablets of ethambutol (25 g). After emergency symptom treatment, she was transferred to a ward where she presented in an irritable state, with orange–red skin and mucus membrane discoloration and slight yellowing of the sclera. The patient’s serum levels of rifampicin (177.2 mg/L), desacetylrifampicin (194.40 mg/L), and ethambutol (13.44 mg/L) were determined. After three cycles of HP and HDF, her serum drug levels had declined to within a normal range, and the color of her skin and mucosa gradually returned to normal. She was discharged from the hospital after a 4-day stay. Ten days after discharge, her follow-up bloodwork indicated normal liver and kidney functioning. Conclusions: HDF and HP are effective at clearing toxic levels of rifampicin. Serum drug concentration monitoring helps accurately guide drug poisoning treatment.

Rationale Concern for drug-drug interactions leading to treatment failure and drug resistant strains have discouraged clinicians from attempting concomitant treatment of hepatitis C (HCV) and Tuberculosis. Increased metabolism of direct-acting antivirals (DAAs) by rifamycins has hindered concurrent use. Development of an assay for ledipasvir and sofosbuvir (LDV/SOF) serum concentrations for therapeutic drug monitoring (TDM) can ensure adequate therapy. Presented are the first cases of concomitant therapy of active TB and HCV with rifamycin containing regimens and DAAs using TDM. Objectives Using TDM, we aim to determine if concomitant therapy with rifamycin containing regimens and DAAs is safe and effective for patients co-infected with TB and HCV. Methods Five individuals with TB and HCV who experienced transaminitis prior to or during TB therapy, were concomitantly treated with rifamycin containing regimens and LDV/SOF. TDM was performed for ledipasvir, sofosbuvir and rifabutin during therapy. Baseline labs and serial liver enzymes were performed. HCV viral load and mycobacterial sputum cultures were obtained upon completion of therapy to determine efficacy of therapy. Measurements and Main Results All patients were found to have nondetectable HCV viral loads and negative mycobacterial sputum cultures upon completion of therapy. No clinically significant adverse effects were reported. Conclusions These cases illustrate concomitant use of LDV/SOF and rifabutin in patients with HCV/TB coinfection. Utilizing serum drug concentration monitoring to guide dosing, correction of transaminitis were achieved which allowed the use rifamycin containing TB therapy. These findings suggest that concomitant therapy of TB/HCV is possible, safe and effective.

Aim: The dose of digoxin is often difficult to be determined precisely. The aim of this study was to retrospectively investigate the effect of blood biochemical indexes on the serum concentration of digoxin. Materials & methods: We collected the data of hospitalized patients treated orally with digoxin in Nanjing Drum Tower Hospital (Nanjing, China) from 2016 to 2018. Descriptive statistics was used to analyze the patients’ comprehensive condition. Results: A total of 425 patients were included in the study. Through analysis, nine factors were included in the regression model of the serum concentration of digoxin, and this regression model showed good predictive performance (r2 = 0.83138; p

Objective:To summarize the results of serum drug concentration monitoring in the Tenth People's Hospital affiliated to Tongji University from 2003 to 2009.Methods:Serum concentrations of sodium valproate(255 cases),phenytoin sodium(33 cases),carbamazepine(48 cases) and digoxin(141 cases) were determined by immune fluorescence polarization method and the results were statistically analyzed.Results:Sodium valproate was the most frequently monitored drug among the three antiepileptic drugs,which accounted for 75.89%,while phenytoin sodium was the least.Serum concentration of carbamazepine of thirty-five cases was within the normal range,accounting for 72.92%(35/48),which was the highest among the three antiepileptic drugs.Serum concentration of digoxin of 114 cases was within the normal range,accounting for 80.85%(114/141).Conclusion:Serum drug concentration monitoring plays an important role in clinic.Its significance should be interpreted in conjunction with clinical manifestation.

Objective—To determine effects of tricyclic antidepressants (TCA) on the ECG of dogs treated for behavioral conditions and to examine correlations between ECG findings and serum concentrations of these medications. Design—Repeated-measures study. Animals—39 client-owned dogs with behavioral problems. Procedure—Two groups of dogs with behavioral problems were evaluated. In group 1 (n = 20), ECG tracings were recorded before starting treatment with TCA and again after treatment for ≥ 1 month. Dogs in group 2 were already on long-term maintenance amounts of antianxiety medication when ECG tracings were recorded and serum concentrations of medications were obtained. Results—Significant differences were not detected for dogs in group 1 between ECG values measured before and after TCA administration. The ECG values for dogs in group 2 did not differ significantly from the mean of group-1 dogs before receiving medication or from the reference range used at our facility. Duration of the P wave had a significant positive correlation with serum concentrations of clomipramine but significant negative correlation with serum concentrations of amitriptyline. The QT interval corrected for heart rate had a significant negative correlation with serum concentrations of amitriptyline. Conclusion and Clinical Relevance—Amitriptyline and clomipramine administered at standard dosages apparently do not cause ECG abnormalities in healthy dogs with behavioral problems. These medications should be used cautiously in dogs with conduction abnormalities, and clinicians should periodically monitor ECG and use good clinical judgment to weigh risks and benefits of medications for the safety of each dog. (J Am Vet Med Assoc 2000;216: 1571–1575)

Objective: The aim of this study was to explore the serum concentration-effect relation for first-line drugs in neuropathic pain and to determine if efficacy could be increased. Methods: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin, and their combination in painful polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0 to 10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography. Results: In 47 patients, pain was reduced -1.0 (95% confidence interval [CI], -1.5 to -0.6) by imipramine, -0.4 (95% CI, -0.9 to 0.1) by pregabalin, and -1.6 (95% CI, -2.1 to -1.1) by combination therapy. On monotherapy, there was no difference between responders and nonresponders with respect to concentrations of imipramine (mean, 161 vs. 229 nmol/L, P=0.129) and pregabalin (mean, 9.8 vs. 11.7 μmol/L, P=0.178). There was no correlation between drug concentration and pain reduction for imipramine (r=0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine < or ≥100 nmol/L, pregabalin < or ≥10 μmol/L) either for monotherapy or for combination therapy (P=0.161 to 0.797). Isobolographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction. Discussion: There were no important relations between drug concentrations and efficacy, or indication of synergistic interaction between the drugs. It was not concluded that treatment can be improved by measurement of drug concentration of pregabalin.

An in vitro pharmacokinetic/pharmacodynamic perfusion model that simulates a two-compartment open model of serum drug concentration-time profiles following intravenous bolus injection and infusion was developed and mathematically described. In the present apparatus model, flow was kept in a one-way mode to avoid liquid traffic, and the washout effect seen in dilution models was overcome by embedding the tested bacteria in low melting point agarose gel. The validity of the equations and the reproducibility of the apparatus model were ascertained by simulating the concentration-time profiles of cefazolin and fosfomycin by substitution of their pharmacokinetic parameters obtained from humans for the equations. An empirical regimen 1X(q24h) of 1 g with cefazolin administered by intravenous infusion effectively killed a Staphylococcus aureus strain. The same regimen with fosfomycin produced a marked kill-curve with a fosfomycin-susceptible enterohaemorrhagic Escherichia coli O157:H7, whereas considerable regrowth was observed with a resistant strain. These results indicated that the present model was able to provide a convenient and reliable method for evaluating the efficacy of antimicrobial agents administered by intravenous infusion., Microbiology and immunology. 51(5), pp.567-575; 2007

The purpose of this study was to document the effect of education on the appropriateness of serum drug concentration (SDC) collection. This study included a period of education for hospital personnel involved in the acquisition of drug levels. These included nursing staff, lab personnel, house-staff (residents/interns), ward clerks, and pharmacists. This study included patients receiving aminoglycoside and/or vancomycin while on the general medicine service during the specified study periods. Patients receiving less than 72 h of antimicrobial therapy and patients transferred to or from the surgery service were excluded from the study. A retrospective pre- and posteducation comparison using Chi-square analysis was made to determine whether the percentage of appropriate and useful SDCs was improved through education. There was a significant difference (p less than 0.005) between the percentage of appropriate SDCs in the pre- and posteducation period. As a result of the study, a change in procedure for ordering SDCs was initiated, using an educational program, in order to continue the trend of appropriate SDCs at the Veterans Administration.

Inpatients who had been in the hospital for more than three years (refractory group, n = 53) were compared with outpatients who had not been admitted to the hospital in the last three years (remission group, n = 42). There were differences between the two groups in "blunted affect-thought disturbance" symptoms, "hallucination-delusion" symptoms, the score of behavior rating scale (BRS), the dosage and serum concentration of antipsychotics, the score of Hasegawa's Dementia Scale (HDS) and brain CT findings. "Blunted affect-thought disturbance" symptoms were strongly related to the BRS score, the dosage of antipsychotics and the HDS score. Sylvian fissures enlargement was related to "blunted affect-thought disturbance" symptoms. Sylvian fissures enlargement was thought to be a biological background of refractory schizophrenia.

The relationship between clinical effects and plasma concentrations of citalopram, fluoxetine, clomipramine, paroxetine and venlafaxine was studied in 119 cases of major depression. Clinical effects were evaluated using the Clinical Global Impression (CGI) improvement scale. Antidepressants were quantified by a separative chromatographic methodology. Plasma concentrations in responder patients were compared with the plasma concentrations proposed in literature as effective values. We found that the usual therapeutic window is convenient for citalopram and clomipramine, but could be reduced for fluoxetine and increased for venlafaxine and paroxetine. Concurrent drug interactions were also evaluated and clomipramine or citalopram plasma levels were found to be influenced by the presence of associated drugs. A larger study is needed, taking into account not only plasma concentrations and clinical effects, but also some pharmacokinetic data, especially the metabolic activity characterising the patient, and the presence or not of associated drugs. Copyright © 2000 John Wiley & Sons, Ltd.

Serum drug concentration measurements can help the practitioner attain maximal therapeutic efficacy and minimal undesirable effects of certain medications. It is necessary, however, to obtain serum samples appropriately to assure that the result will provide useful information. In preparation for expansion of clinical pharmacy services to the surgical ICU, a study was performed to a) identify the drugs for which serum samples were requested and b) assess whether the results of the serum samples were being used appropriately to adjust doses. Currently, the pharmacy pharmacokinetics service routinely analyzes serum concentrations for antimicrobial agents, theophylline, and other drugs as requested. By the end of this year, we expect further expansion to include phenytoin, pentobarbital, phenobarbital, procainamide/NAPA, lidocaine, and digoxin.