Gender difference in letrozole pharmacokinetics in rats.
OBJECTIVE
To study gender difference in letrozole (Letr) pharmacokinetics in rats.


METHODS
Letr concentrations in plasma and tissues were determined after ig administration of Letr 2 mg/kg. Recoveries of Letr in urine and feces were also analyzed.


RESULTS
Marked gender differences were found 6 h after ig Letr 2 mg/kg, the plasma concentrations of Letr in male rats were significantly (P < 0.01) lower than those in female rats. For example, at 24, 36, 48, and 72 h after administration, plasma concentrations in female rats were about 3.3, 5.6, 10.5, and 7.4-fold of that of male rats, respectively. AUC value of Letr in male was only about one-third of that in female rats. Estimated terminal phase half-lives (T1/2) were 10.5 and 40.4 h, respectively. In female rats, cumulative excreted fractions of Letr in urine and feces were 5.8% +/- 1.4% and 6.6% +/- 1.1% within 120 h after administration, respectively, but in male rats, the excreted fractions of Letr in urine and feces were only 1.30% +/- 0.59% and 0.87% +/- 0.31%. Letr concentrations in female rat tissues were significantly (P < 0.01) higher than those in male rat tissues 24 h after administration.


CONCLUSIONS
There are marked gender differences in Letr pharmacokinetics in rats.
Liu
X D
XD
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. xdliu@jlonline.com
Xie
L
L
Zhong
Y
Y
Li
C X
CX
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D001141:Aromatase / Q000493:pharmacokinetics; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014018:Tissue Distribution; D014230:Triazoles / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D001141:Aromatase