The CYP2C19 genotype and the use of oral contraceptives influence the pharmacokinetics of carisoprodol in healthy human subjects.

Aims: The aim of the present study was to investigate if subjects with one normal and one non-functional CYP2C19 allele (intermediate metabolizers; IMs) metabolized carisoprodol differently than individuals with two normal CYP2C19 alleles (extensive metabolizers; EMs) We also wanted to investigate whether the use of oral contraceptives influences the metabolism of carisoprodol in EMs and IMs. Impairing effects on psychomotor coordination and feelings of sedation were studied by comparing IMs with EMs following their ingestion of a single dose of 700 mg carisoprodol.

Methods: Thirty-seven healthy Caucasian volunteers participated in the study, of whom 25 were not using any drugs known to interact with CYP2C19, including two poor metabolizers (PMs) (CYP2C19 *2/*2 or CYP2C19 *2 /*4), 11 IMs (CYP2C19 *1/*2 or CYP2C19 *1/*4) and 12 EMs (CYP2C19 *1/*1); the remaining 12 participants were six EMs and six IMs using oral contraceptives.

Pharmacokinetics of trimeprazine in children.

The pharmacokinetics of trimeprazine (alimemazine) were studied over 24 hr in six children after a recommended preanaesthetic oral dose of 3 mg.kg-1. The degree of sedation before anaesthesia was evaluated.

The effect of ethanol intake on propoxyphene absorption and biotransformation in dogs.

The effect of ethanol (0.5 and 1.0 g/kg) on gastrointestinal absorption and presystemic biotransformation of propoxyphene (4 mg/kg) was studied in dogs in a crossover design.

Ethanol does not increase lethality due to propoxyphene in rats.

Male Wistar rats (210-330 g) were used as test animals. Propoxyphene (175 mg/kg) and ethanol (2 g/kg) were administered by gastric intubation, naloxone (2 mg/kg) by subcutaneous injection. Four groups, each consisting of 19 rats received either of the following drug treatments: Propoxyphene; ethanol + propoxyphene; naloxone + propoxyphene; and naloxone + ethanol + propoxyphene.