title: Antipyrine metabolism is not affected by terbinafine, a new antifungal agent.
abstract: The potential to inhibit drug metabolism of the new antifungal agent terbinafine has been studied using antipyrine (single oral dose of 10 mg/kg) as a probe drug. In a cross-over study in 8 healthy volunteers, antipyrine was administered prior to, during and after 8 days of oral terbinafine 125 mg b.d. Antipyrine, its major metabolites 4-hydroxyantipyrine (4-OH-AP), 3-hydroxymethylantipyrine (3-OH-CH3-AP) and norantipyrine (Nor-AP) were analyzed by specific HPLC assays in multiple plasma and urine samples. During all three parts of the study, the pharmacokinetics of antipyrine viz. t1/2 (11.7 h), total plasma (38.5 ml.h-1.kg-1) and renal clearance (1.6 ml.h-1.kg-1), and its clearance rates to metabolites (CLM), eg. CLM for 4-OH-AP (12.3 ml.h-1.kg-1), CLM for 3-OH-CH3-AP (4.2 ml.h-1.kg-1) and CLM for Nor-AP (6.7 ml.h-1.kg-1) did not differ from the control values. Thus, all the cytochrome P-450-dependent isozymes involved in the metabolism of antipyrine and many other drugs should not be affected by therapeutic doses of terbinafine.
authors.affiliation: Dr. Margarete-Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Federal Republic of Germany.
authors.forename: R
authors.initials: R
authors.lastname: Seyffer
authors.forename: M
authors.initials: M
authors.lastname: Eichelbaum
authors.forename: J C
authors.initials: JC
authors.lastname: Jensen
authors.forename: U
authors.initials: U
authors.lastname: Klotz
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D000983:Antipyrine / Q000378:metabolism* / Q000493:pharmacokinetics; D001711:Biotransformation; D005260:Female; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology*; D000077291:Terbinafine
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine; D000983:Antipyrine