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Olaparib, an oral poly-ADP ribose polymerase (PARP) inhibitor, is a relatively new anticancer drug. It is essential to find TDM-guided dosage for better safety and tolerability. However, first, it is important to develop a suitable analytical method to conduct reliable TDM. The aim of the study was the validation of the UPLC-MS/MS method for TDM of olaparib in patients with ovarian cancer, with particular attention to recovery optimization. Validation of the method under analysis were done in accordance with the ICH guidelines. The recovery of olaparib was optimized with the Central Composite Design (CCD). The TDM study was conducted on 10 patients with ovarian cancer treated with olaparib. The method validation was characterized by good precision (CV < 9.09%), accuracy (89.23-111.08%), and linearity (r = 0.9993) within the range of 100-20,000 ng/mL, with limits of detection of 30 ng/mL. The 10-minute shaking time combined with 100% acetonitrile resulted in an estimated value of 98% for recovery and the observed value of 98%. The olaparib concentrations in the patients’ plasma were 1078.2-16773.8 ng/ mL. A wide range of olaparib concentrations was observed in patients reporting adverse reactions, which included anemia (grade 1, n = 2), neutropenia (grade 1, n = 1), and creatinine increased (grade 1, n = 1). The method validation included all the required procedures showing that the measurement of olaparib concentrations in the plasma was reliable for the intended application, such as TDM. [ABSTRACT FROM AUTHOR]

Tapentadol (TAP) is the first representative of a new class of multimodal analgesics with a favorable safety profile, also applicable in postoperative pain. As a UDP-glucuronosyltransferase (UGT) substrate (in about 70%), TAP pharmacokinetics can potentially be influenced by UGT inducers or inhibitors. It is known that smoking can increase drug metabolism activity through UGT enzyme induction. Therefore, the study aimed to evaluate the pharmacokinetics of TAP after open abdominal hysterectomy (AH) in smoking compared to non-smoking tobacco patients. A single oral dose of TAP 100 mg was given to the patients on the first postoperative day after AH (n = 6, smoking and n = 8, non-smoking patients). Pain relief (Numerical Rating Scale, NRS), sedation, saturation, heart rate, and adverse effects were monitored. Blood samples were collected within 12 h after the drug administration. Smokers presented significantly lower Cmax and AUC0-t, and CL/F value was twice as high in this group. A moderately strong negative correlation between NRS scores and TAP concentration was revealed (R2=-0.5231). Negative correlations between TAP concentration and life parameters: oxygen saturation and heart rate were observed. Significantly lower plasma concentrations and exposure to TAP in smoking patients after AH compared to non-smoking may indicate metabolic induction of UDP-glucuronosyltransferase by components of tobacco smoke. Since plasma concentration of TAP and NRS are negatively correlated, this may require consideration of TAP dose adjustments in smoking patients. [ABSTRACT FROM AUTHOR]

Objective. Systemic inflammation may change the bioavailability and pharmacokinetics of opioids. However, there are insufficient data on morphine pharmacokinetics in mild inflammatory conditions. This study aimed to determine the pharmacokinetics of morphine during low-dose endotoxemia in rabbits. Design. In two experiments (separated by a 14-day washout period), 10 rabbits received intravenous morphine at a dose of 3 mg/kg. In the second set of experiments, morphine infusion was preceded by low-dose endotoxemia induced with lipopolysac-charide (Escherichia coli 0111:B4) at a dose of 5 mg/ kg. The kinetics of systemic morphine concentrations and chosen physiological parameters were measured at specific time intervals up to 6 hours after morphine administration. Results. In endotoxemia, decreased elimination half-life (P = 0.017), mean residence time (P = 0.022), and volume of distribution (P = 0.037) as well as an increased elimination rate constant (P = 0.013) and total body clearance (P = 0.023) were noted. The inverse linear correlation between morphine clearance versus the percentage (%) change in body temperature and pulse rate observed under control conditions was abolished under endotoxemia. Conclusions. Low-dose endotoxemia is correlated with significant alterations in morphine pharmacokinetics in rabbits, leading to the faster elimination of the drug. Clinical Implications. These findings may have important implications in patients with low-grade inflammation and imply the need to modify morphine dosing regimens to ensure optimal analgesia. The issue warrants further experimental and clinical investigation. [ABSTRACT FROM AUTHOR]

The aim of this study was an in vitro - in vivo evaluation of a new oral dosage form of tramadol hydrochloride (TH), controlled-release capsules filled with coated pellets, 100 mg (TC), compared to the sustained release tablets, Tramal Retard, 100 mg (TR). In vitro release study of both formulations showed a similar release profile of TH over 8 h (f2 was 52). In vivo study (single oral, 100 mg dose administration in 8 rabbits) showed that the amount of TH absorbed into the systemic circulation after TC and TR administration was also similar (90% CI for AUC(0-t) and AUC(0-infinity) were 90-124% and 97-109%, respectively). However, a comparison of AUC(0-t) of pharmacokinetics of TC and TR indicates significantly prolonged absorption and elimination processes of TH when the drug is given in controlled-release capsules filled with coated pellets. It was manifested by longer: mean absorption time (p = 0.0016), mean residence time (p = 0.0268), absorption half-life (p = 0.0016), elimination half-life (p = 0.0493) and lower: absorption rate constant (p = 0.0016), elimination rate constant (p = 0.0148) and total body clearance Cl/F (p = 0.0076). It may be concluded that the new TH formulation could be expected to have a more prolonged analgesic activity than commercial sustained release tablets.

The study concerned the stability of calcium folinate in concentrate in glass vials and diluted in polyethylene (PE) bags stored at 15-25 degrees C and 2-8 degrees C for up to 34 days. Original vials of calcium folinate injection (10 mg/mL, Teva) were stored at room and refrigerator temperatures and subjected to re-piercing at 1, 2, 3, 7, 14, 22, 28, 30 and 34 days following the initial piercing. Calcium folinate infusions at nominal concentrations of 0.12 mg/mL were prepared in 0.9% sodium chloride (250 mL) in PE bags. Chemical stability was measured with a stability-indicating high-performance liquid chromatography (HPLC) assay. Physical stability was assessed by visual inspection in normal light. The concentration of calcium folinate at each sampling time in the analyzed solutions remained > 90% of the initial concentration, regardless of the container. No changes in color or turbidity were observed in any of the vials or in the prepared solutions. Calcium folinate, both undiluted in glass containers and diluted with NaCl 0.9% in PE bags, remains stable (< 10% degradation) for at least 30 days at room and refrigerator temperatures when protected from light.

Aim of the Study: The subject of study was the stability of cisplatin in concentrate in glass vials and diluted in polyethylene (PE) bags stored at 15-25°C for up to 30 days., Material and Methods: Original vials of cisplatin injection (1 mg/ml, Teva) were stored at room temperature and subjected to re-piercing after 1, 2, 3, 7, 14, 21, 28 and 30 days following the initial piercing. Cisplatin infusions at nominal concentrations of 0.1 mg/ml were prepared in 0.9% sodium chloride (1000 ml) in PE bags. Chemical stability was measured by means of a stability-indicating high-performance liquid chromatography (HPLC) assay. Physical stability was assessed by visual inspection in normal light., Results: The concentration of cisplatin at each sampling time in the analysed solutions remained within 92.0-100.7% of initial concentration, regardless of the container. No changes in colour or turbidity were observed in any of the vials or prepared solutions., Conclusions: Cisplatin, both undiluted in glass containers and diluted with NaCl 0.9% in PE bags, remains stable (< 10% degradation) for at least 30 days at room temperature when protected from light.