The effect of sex and age on caffeine pharmacokinetics in cattle.

Abstract

The aim of this study was to determine the effect of sex on the pharmacokinetics of caffeine in cattle at different ages. Ten female and 10 male Holstein cattle were subject to a caffeine test when they were aged 1, 2, 4, 6, 8, 12 and 18 months. Caffeine, 5 mg kg(-1)body weight, was given intravenously as a sterile isotonic solution. An automated, enzyme-multiplied, immunoassay technique (EMIT) was used to determine plasma caffeine concentration. The volume of distribution of caffeine (V(SS)) decreased significantly between 1 and 18 months of life. Mean V(SS)values observed in males and females were not statistically different. The experimental period was characterised by a steady decrease (statistically significant) in caffeine mean residence time (MRT). These values did not differ significantly between males and females under 8 months of age. In 8-, 12- and 18-month-old animals, the caffeine MRT in the females was significantly shorter than in the males. The total plasma clearance (Cl(tot)) of caffeine increased significantly between 1 and 18 months of age. No significant differences were observed between total plasma clearance of caffeine in males and females under 8 months of age. In 8-, 12- and 18-month-old animals, the Cl(tot)of caffeine was significantly higher in females than in males. In conclusion, we report a sex-linked difference in pharmacokinetics of caffeine in cattle over 8 months of age, the females being the more active metabolisers. The results of the present study support the hypothesis that the metabolism of xenobiotics is sexually different in ruminants.