Antipyrine metabolism is not affected by terbinafine, a new antifungal agent

Summary

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. t_1/2 (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 (CL_M), eg. CL_M for 4-OH-AP (12.3 ml·h⁻¹·kg⁻¹), CL_M for 3-OH-CH₃-AP (4.2 ml·h⁻¹·kg⁻¹) and CL_M 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.