A DBS method for quantitation of the new oral trypanocidal drug fexinidazole and its active metabolites.

Aim: Fexinidazole (FEX) is a nitroimidazole being developed as a new trypanocide treatment for human African trypanosomiasis/sleeping sickness. Its main metabolites, fexinidazole sulfoxide (M1) and fexinidazole sulfone (M2), show the same in vitro pharmacological activity as FEX.

Methods & Results: An LC-MS/MS assay was developed for quantitation of FEX in DBS, collected via finger-prick from healthy subjects.

Dried Blood Spot Methodology in Combination With Liquid Chromatography/Tandem Mass Spectrometry Facilitates the Monitoring of Teriflunomide.

Background: Teriflunomide, a once-daily oral immunomodulator approved for treatment of relapsing-remitting multiple sclerosis, is eliminated slowly from plasma. If necessary to rapidly lower plasma concentrations of teriflunomide, an accelerated elimination procedure using cholestyramine or activated charcoal may be used. The current bioanalytical assay for determination of plasma teriflunomide concentration requires laboratory facilities for blood centrifugation and plasma storage.

A phase I open-label study investigating the disposition of [14C]-cabazitaxel in patients with advanced solid tumors.

Cabazitaxel is a semisynthetic taxane approved for the treatment of patients with hormone-refractory metastatic prostate cancer (now known as metastatic castration-resistant prostate cancer) treated previously with a docetaxel-containing treatment regimen. The human plasma pharmacokinetics of cabazitaxel have been described previously, but detailed analyses of the metabolism and excretion pathways of cabazitaxel have not yet been published. Metabolite profiling, quantification, and identification as well as excretion analyses were carried out on samples from patients with advanced solid tumors who received an intravenous infusion of 25 mg/m [C]-cabazitaxel (50 μCi, 1.

Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis.

Aim: To assess the bioequipotency of equimolar doses of idraparinux (2.5 mg) and idrabiotaparinux (3.0 mg).

Phase I pharmacokinetic, food effect, and pharmacogenetic study of oral irinotecan given as semisolid matrix capsules in patients with solid tumors.

Purpose: To characterize the maximum-tolerated dose, recommended dose, dose-limiting toxicities (DLT), pharmacokinetic profile, and food effect of orally administered irinotecan formulated as new semisolid matrix capsules.

Experimental Design: Irinotecan was given orally in fasted patients once daily for 5 consecutive days and repeated every 3 weeks. Patients were randomly assigned to take the drug along with a high-fat, high-calorie breakfast for the administration at day 1 of the first or second cycle.

Phase I and pharmacokinetic study of oral irinotecan given once daily for 5 days every 3 weeks in combination with capecitabine in patients with solid tumors.

Purpose: To assess the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and preliminary antitumor activity of oral irinotecan given in combination with capecitabine to patients with advanced, refractory solid tumors.

Patients And Methods: Patients were treated from day 1 with irinotecan capsules given once daily for 5 consecutive days (50 to 60 mg/m2/d) concomitantly with capecitabine given twice daily for 14 consecutive days (800 to 1,000 mg/m2); cycles were repeated every 21 days.

Results: Twenty-eight patients were enrolled and received 155 cycles of therapy (median, five cycles; range, one to 18 cycles).

Phase I study of an oral formulation of irinotecan administered daily for 14 days every 3 weeks in patients with advanced solid tumours.

A phase I study was conducted with oral irinotecan given daily for 14 days every 3 weeks in 45 patients with solid tumours to establish the maximum tolerated dose (MTD), toxicity, preliminary antitumour response and pharmacokinetics. Irinotecan was administered orally as a powder-filled capsule at doses ranging from 7.5 to 40 mg/m2 per day.

Reliable anticoagulation with enoxaparin in patients undergoing percutaneous coronary intervention: The pharmacokinetics of enoxaparin in PCI (PEPCI) study.

The objective of this study was to evaluate the pharmacokinetic response to intravenous (IV) enoxaparin given 8-12 hr after subcutaneous (SC) dosing in patients undergoing percutaneous coronary intervention (PCI). Fifty-five patients received SC enoxaparin (1 mg/kg every 12 hr) followed by an IV bolus (0.3 mg/kg) 8-12 hr after the last SC dose, at the start of PCI or during catheterization.

Population pharmacokinetics and pharmacodynamics of enoxaparin in unstable angina and non-ST-segment elevation myocardial infarction.

Aims: A major concern with any antithrombotic therapy is an increase in the risk of haemorrhage. The aim of this study was to analyse population pharmacokinetics and pharmacokinetic/pharmacodynamic (PK/PD) relationships for enoxaparin in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI), which may help predict risk of haemorrhage.

Methods: Anti-factor Xa (anti-Xa) activity was measured as marker of enoxaparin concentration in 448 patients receiving the drug as a single 30-mg intravenous bolus followed by 1.

Dosage adjustment and pharmacokinetic profile of irinotecan in cancer patients with hepatic dysfunction.

Purpose: To determine the recommended dose (RD) and the pharmacokinetic profile of irinotecan and its metabolites in cancer patients with hyperbilirubinemia.

Patients And Methods: Patients were assigned to four treatment groups according to their baseline total bilirubin level. Patients in group I (bilirubin within normal range) and group II (bilirubin 1.

The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers.

Objectives: The objective of this study was to compare the pharmacokinetics of the low-molecular-weight heparin enoxaparin in obese and nonobese volunteers, by means of two administration regimens.

Methods: Enoxaparin was administered subcutaneously (1.5 mg/kg once daily for 4 days) and in a single 6-hour infusion (1.

Pharmacokinetics and pharmacodynamics of the prophylactic dose of enoxaparin once daily over 4 days in patients with renal impairment.

The pharmacokinetics of the low-molecular-weight heparin enoxaparin were evaluated in 12 healthy volunteers and 36 patients with mild, moderate or severe renal impairment. Enoxaparin was administered once daily by subcutaneous injections at a dose of 40 mg for 4 days and venous blood samples were taken over a 5-day period to determine antifactor Xa and antifactor IIa activity and the activated partial thromboplastin time. Adverse events were also recorded.