Population pharmacokinetics of cabazitaxel in patients with advanced solid tumors.

Purpose: To develop a population pharmacokinetic (PK) model for cabazitaxel in patients with advanced solid tumors and examine the influence of demographic and baseline parameters.

Methods: One hundred and seventy patients who received cabazitaxel (10-30 mg/m(2), 1-h IV infusion) every 7 or 21 days in five Phase I-III studies were analyzed by non-linear mixed-effect modeling (NONMEM VI). Model evaluation comprised non-parametric bootstrap and visual predictive checks.

Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits Δ9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans.

Aim: Cannabinoid receptor type 1 (CB1 ) antagonists have been developed for the treatment of obesity and associated risk factors. Surinabant is a high affinity CB1 antagonist in vitro. The aim of this study was to assess the magnitude of inhibition by surinabant of CNS effects and heart rate induced by Δ(9) -tetrahydrocannabinol (THC) in humans.

Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women.

Objective: This study aimed to evaluate the pharmacokinetics, pharmacodynamics and safety of the nonsteroidal progesterone receptor agonist, tanaproget.

Methods: A randomized, double-blind, placebo-controlled, sequential-group study of ascending single doses of tanaproget was conducted in healthy, 25- to 45-year-old women on cycle days 8 to 12. Eight subjects (six active, two placebo) per cohort received a dose of 0.

Excretion of pantoprazole in human breast.

Objective: To measure the amount of pantoprazole in human milk following its oral administration to a breast-feeding mother and to estimate human exposure.

Study Design: One woman was studied over a 24-hour interval after oral administration of 40-mg pantoprazole. Serial plasma and milk samples were collected over 24 hours, and pantoprazole concentrations were measured by high-performance liquid chromatography.

Oral bioavailability of pantoprazole suspended in sodium bicarbonate solution.

The bioavailability of pantoprazole when administered as a suspension in sodium bicarbonate solution and as the oral tablet was studied. In an open-label, randomized, two-period crossover study, healthy fasting subjects received either one enteric-coated 40-mg pantoprazole tablet by mouth with 240 mL of water or 20 mL of a suspension prepared from one crushed pantoprazole tablet and 840 mg of sodium bicarbonate solution and administered via a nasogastric tube. Treatments were separated by a 48-hour washout period.

Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects.

Aims: To evaluate potential pharmacokinetic interactions between phenobarbitone and retigabine, a new antiepileptic drug.

Methods: Fifteen healthy men received 200 mg of retigabine on day 1. On days 4-32, phenobarbitone 90 mg was administered at 22.

Quantitation of cytochrome P450 mRNA levels in human skin.

There is considerable interindividual variation in man's ability to metabolize drugs and foreign compounds. These differences can partly be attributed to genetic polymorphisms that result in the generation of multiple phenotypes with different drug-metabolizing capabilities. Genetically derived differences can easily be assessed by genotyping assays in cases where the polymorphism has been identified.

Effects of age and sex on the disposition of retigabine.

Background: The novel antiepileptic drug retigabine is the first selective M-current potassium channel opener for KCNQ2/3 and KCNQ3/5 channels. Retigabine undergoes phase II metabolism (N-glucuronidation, acetylation) exclusively and renal excretion.

Objective: Our objective was to evaluate the effects of age and sex on the pharmacokinetics of retigabine.

Proton pump activation in stimulated parietal cells is regulated by gastric acid secretory capacity: a human study.

Under normal physiological conditions, gastric acid production is controlled by a negative feedback mechanism. Proton pump inhibitors, such as pantoprazole, inhibit gastric acid secretion by irreversibly binding and inactivating luminally active hydrogen potassium ATPase. Recovery of acid production after treatment with a proton pump inhibitor is driven by new pump synthesis, activation of existing cytoplasmic pumps, or reversal of proton pump inhibition.

Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in healthy volunteers.

Retigabine, a first-in-class selective M-current potassium channel opener, is a novel antiepileptic compound currently in clinical development. The purpose of this randomized placebo-controlled study was to assess retigabine oral safety and pharmacokinetics in healthy male volunteers (N = 45). Subjects received one dose on day 1 and doses every 12 hours for the next 14 days.