Premium
The effect of tamoxifen on the pharmacokinetics of letrozole in female rats
Author(s) -
Tao X.,
Brodie A. M. H.,
Nnane I. P.
Publication year - 2006
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.514
Subject(s) - letrozole , pharmacokinetics , bioavailability , tamoxifen , volume of distribution , antiestrogen , pharmacology , chemistry , absorption (acoustics) , distribution (mathematics) , endocrinology , medicine , cancer , breast cancer , mathematical analysis , physics , mathematics , acoustics
Abstract The effects of single doses of tamoxifen (TAM; 0.5–5 mg/kg, i.v.) and chronic pretreatment with TAM (0.1–5.0 mg/kg/day, i.p. for 7 consecutive days) on letrozole (0.5 mg/kg, i.v.) pharmacokinetics were evaluated in female Sprague‐Dawley rats. The plasma concentration‐time profiles of letrozole (0.1–2.0 mg/kg) after single i.v. doses were analysed by the non‐compartment model with terminal half‐lives (t 1/2,λz ) ranging from 34.3 to 37.5 h. The volume of distribution at the terminal phases (V d(λz) ) ranged from 1.9 to 2.1 l/kg and clearance ( CL ) varied from 0.036 to 0.042 l/(h·kg). After co‐administration of TAM and letrozole intravenously, the t 1/2 , V d(λz) and CL of letrozole were not significantly altered. Chronic pretreatment with TAM significantly decreased the t 1/2 of letrozole by about 33%, and increased its clearance by an average of 40%. However, TAM pretreatment did not significantly affect the V d(( λ z) of letrozole in female rats. Co‐administration of letrozole and TAM orally increased the absorption half‐life of letrozole threefold although the absolute bioavailability remained unchanged. These observations suggest that single oral doses of TAM delay the absorption of letrozole while chronic pretreatment with TAM accelerates the elimination of letrozole, probably due to induction of cytochrome P450 enzymes in rats. Copyright © 2006 John Wiley & Sons, Ltd.