Evaluation of early fetal exposure to vaginally-administered metronidazole in pregnant cynomolgus monkeys.

Given concern about potential embryo-fetal harm following seminal exposure to drugs with teratogenic potential, pharmaceutical companies use theoretical calculations to estimate seminal concentrations, maternal exposure, and distribution across the placenta to the embryo-fetal compartment for risk assessment. However, it is plausible that there are additional mechanisms whereby the conceptus is exposed. In order to determine if theoretical calculations are sufficiently conservative to predict embryo-fetal exposure from drugs in semen, pregnant cynomolgus monkeys were given a vaginal dose of metronidazole during the early fetal period and cesarean-sectioned.

Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States.

Purpose: Systemic exposure to rosuvastatin in Asian subjects living in Japan or Singapore is approximately twice that observed in Caucasian subjects in Western countries or in Singapore. This study was conducted to determine whether pharmacokinetic differences exist among the most populous Asian subgroups and Caucasian subjects in the USA.

Method: Rosuvastatin pharmacokinetics was studied in Chinese, Filipino, Asian-Indian, Korean, Vietnamese, Japanese and Caucasian subjects residing in California.

Pharmacokinetic and pharmacodynamic profile of rosuvastatin in patients with end-stage renal disease on chronic haemodialysis.

Background: Rosuvastatin has been shown to provide effective treatment of dyslipidaemia in patients with end-stage renal disease (ESRD) undergoing haemodialysis, but data from controlled trials are very limited on the pharmacokinetics and pharmacodynamics of rosuvastatin in this population.

Objective: The aim of the present study was to better define the pharmacokinetic and pharmacodynamic profiles of repeated doses of rosuvastatin at a starting dose of 10 mg/day in a group of patients with ESRD.

Study Design: This was a single-centre, open-label study of rosuvastatin 10 mg daily, given over a 16-day treatment period in patients with ESRD undergoing chronic haemodialysis.

Predicting the drug interaction potential of AMG 853, a dual antagonist of the D-prostanoid and chemoattractant receptor-homologous molecule expressed on T helper 2 cells receptors.

2-(4-(4-(tert-Butylcarbamoyl)-2-(2-chloro-4-cyclopropylphenylsulfonamido)phenoxy)-5-chloro-2-fluorophenyl)acetic acid (AMG 853) is an orally bioavailable and potent dual antagonist of the D-prostanoid and chemoattractant receptor-homologous molecule expressed on T helper 2 cells receptors. The drug interaction potential of AMG 853, both as a victim and a perpetrator, was investigated using in vitro, in silico, and in vivo methodologies. Experiments in human liver microsomes (HLM) and recombinant enzymes identified CYP2C8, CYP2J2, and CYP3A as well as multiple UDP-glucuronosyltransferase isoforms as being responsible for the metabolic clearance of AMG 853.

Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment.

Background: Systemic exposure to rosuvastatin had been observed to be approximately 2-fold higher in Japanese subjects living in Japan compared with white subjects in Western Europe or the United States. The organic anion transporting polypeptide 1B1 contributes to the hepatic uptake of rosuvastatin. Polymorphisms in the SLCO1B1 gene can lead to reduced transport function in vitro (T 521>C).

The effect of gemfibrozil on the pharmacokinetics of rosuvastatin.

Background: Coadministration of statins and gemfibrozil is associated with an increased risk for myopathy, which may be due in part to a pharmacokinetic interaction. Therefore the effect of gemfibrozil on rosuvastatin pharmacokinetics was assessed in healthy volunteers. Rosuvastatin has been shown to be a substrate for the human hepatic uptake transporter organic anion transporter 2 (OATP2).