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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]

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The prognosis for patients with acute myeloid leukemia (AML) varies depending on genetic factors. The presence of mutations in the FMS-like tyrosine kinase 3 (FLT3) gene is found in approximately 30% of AML patients. Midostaurin, a first-generation multi-targeted tyrosine kinase inhibitor, is the first FLT3 inhibitor approved for the treatment of newly diagnosed AML patients with the FLT3 mutation in combination with standard induction and consolidation chemotherapy. However, as numerous clinical trials have shown, the list of indications for this drug is likely to be extended. Midostaurin can be administered orally, which improves the patient's comfort during treatment. In general, it has a favorable safety profile, but interactions with other drugs, such as strong CYP3A4 inhibitors or inducers, which are often used in the concomitant therapy of AML patients, may lead to changes in midostaurin plasma concentrations. In consequence, such interactions may increase the toxicity of the treatment or reduce its therapeutic effect. This review aims to summarise the current knowledge on midostaurin, i.e. its mechanisms of action, dosage, adverse effects, mechanisms of resistance, and limitations to its use. Due to the growing importance of the management of drug-drug interactions mediated via cytochrome CYP3A4, the main focus of this study is the pharmacokinetics of midostaurin and the variability of its plasma concentrations. The authors emphasize therapeutic drug monitoring with midostaurin as a potential method of managing AML patients with FLT3 mutation. [ABSTRACT FROM AUTHOR]

Paracetamol is one of the most common analgesic and antipyretic drugs. Recently intravenous paracetamol has been widely used to treat moderate postoperative pain. Surgery is the main method of treatment of renal cancer. Total or partial nephrectomy can be performed, depending on the size and location of the tumor. Pharmacokinetics of drugs may depend on the type of surgery. The aim of the study was to compare the postinfusion pharmacokinetics of paracetamol in patients after total nephrectomy (TN) and nephron sparing surgery (NSS).The research was carried out on two groups of patients after nephrectomy: total (TN n = 37; mean [SD], age, 60.4 [10.9] years; BMI, 26.5 [3.8] kg/m2; creatinine clearance, Cl, 80.9 [37.1] mL/min) and nephron sparing surgery (NSS n = 17; 57.9 [16.5] years; BMI, 29.5 [5.3] kg/m2; Cl, 97.6 [27.8] mL/min). The patients were treated with paracetamol (PerfalganO Bristol-Myers Squibb) at an intravenous dose of 1.000 mg, which was infused for 15 minutes after surgery. The concentrations of paracetamol in the patients' plasma were determined by the HPLC method with UV detection (X = 261 run). The main pharmacokinetic parameters of paracetamol in the TN vs. NSS group were as follows: C.. 29.08 [17.39] vs. 27.54 [15.70] pg/mL (p = 0.6692); AUC5, 29.24 [13.86] vs. 34.85 [14.28] pg.h/mL (p = 0.2896); AUMC5,,,, 47.58 [26.08] vs. 62.02 [27.64] pg-h/mL (p = 0.1345); to. 2.34 [0.96] vs. 1.93 [0.50] h (p = 0.1415), respectively. In both groups the exposure to paracetamol was comparable. The t1/2 after nephron sparing surgery was shorter than after total nephrectomy. Therefore, these patients may demand more frequent drug administration. In the NSS group the C. of the analgesic was considerably reduced in men.

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.