title: The effect of midazolam administration on the pharmacokinetics of antipyrine in the rat.
abstract: 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.
authors: Department of Pharmacokinetics and Metabolism, Roche Products Limited, Welwyn Garden City, Herts, UK.
authors: S M
authors: SM
authors: White
authors: J G
authors: JG
authors: Allen
authors: J F
authors: JF
authors: Altman
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000008:administration & dosage*; D051381:Rats
chemical_list: D008874:Midazolam; D000983:Antipyrine