The effect of midazolam administration on the pharmacokinetics of antipyrine in the rat
| Autor: | S. M. White, J. G. Allen, J. F. B. Altman |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Male
Metabolic Clearance Rate medicine.drug_class Midazolam Health Toxicology and Mutagenesis Pharmacology Toxicology Biochemistry Hypnotic Pharmacokinetics Oral administration medicine Animals Enzyme inducer Dose-Response Relationship Drug biology business.industry General Medicine Drug interaction Rats Kinetics biology.protein Phenobarbital business Antipyrine After treatment Half-Life medicine.drug |
| Zdroj: | Xenobiotica. 17:869-873 |
| ISSN: | 1366-5928 0049-8254 |
| Popis: | 1. The clearance and elimination half-lives for i.v. doses of antipyrine were determined in 6 groups of 6 male CD rats with no prior treatment, then again following 7 days treatment with graded oral doses of midazolam, and finally after 3 i.p. doses of phenobarbitone. 2. Substantial increases in clearance and decreases in half-lives were observed following phenobarbitone treatment, demonstrating that antipyrine provides a reliable index of enzyme induction. 3. After treatment with midazolam, maximal induction was seen in animals dosed at 27 or 80 mg/kg per day; an intermediate effect was found with 9 mg/kg per day and no effect at 0.2 and 1.0 mg/kg per day. 4. The results indicate that there is a substantial margin of safety between the proposed human therapeutic doses (7.5 to 15 mg/day) and the minimum effective dose that leads to enzyme induction in laboratory animals. |
| Databáze: | OpenAIRE |
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