Influence of sex on the pharmacokinetics of tolmetin in the rat.
The purpose of this study was to investigate sex-related differences in the pharmacokinetics of tolmetin, a potent nonsteroidal anti-inflammatory drug, in the rat. Male and female Wistar rats received oral tolmetin at two dose levels, 3.2 and 10 mg/kg. Blood samples were drawn at selected times after drug administration, and tolmetin concentration in whole blood was determined. Tolmetin was rapidly absorbed in all cases. C(max) increased with the dose, but was similar in both sexes. Notwithstanding, tolmetin half-life was significantly prolonged in females compared with males. As a result of the prolonged half-life, area under the curve values were significantly higher in females than in males. Tolmetin clearance was significantly reduced in females. The present results strongly suggest sex-related differences in the pharmacokinetics of tolmetin in the rat. Tolmetin elimination appears to be impaired in females, compared with males. The existence of sex-related differences in tolmetin pharmacokinetics in other species, including humans, requires further investigation.
Facultad de Ciencias Químicas, Benemérita Universidad de Puebla, Mexico.
M
M
Jiménez
J
J
Pérez-Urizar
F J
FJ
Flores-Murrieta
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D014046:Tolmetin / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003577:Cytochrome P-450 Enzyme System; D014046:Tolmetin