Abstract
The purpose of this study was to investigate the effect of breed on the pharmacokinetics and metabolism of caffeine (CF) and the hepatic metabolic capacity in sheep. CF was administered as a single dose of 5 mg/kg b.w. by the intravenous in Morkaraman (MK), Akkaraman (AK) and Anatolia Merino (AM) sheep breeds. The plasma levels of CF and its primary metabolites-theobromine (TB), paraxanthine (PX) and theophylline (TP) were measured using high-performance liquid chromatography. Pharmacokinetic parameters of CF and its metabolites were calculated. Plasma TB+PX+TP/CF metabolic ratio was determined as an alternative to CF clearance for the determination of hepatic metabolic capacity in practice. In three breeds, all kinetic parameters of CF were different significantly (P<0.05) except volume of distribution. Elimination of CF was slow in MK (ClT; 0.03 ± 0.01 l hr/kg, t1/2λz; 15.74 ± 7.35 hr) and AM (ClT; 0.05 ± 0.02 l hr/kg, t1/2λz; 9.68 ± 5.21 hr) breeds when compared to AK breed (ClT; 0.08 ± 0.01 l hr/kg, t1/2λz; 6.84 ± 0.79 hr). There was significant correlation (r2=0.904, P<0.01) between CF clearance and plasma TB+PX+TP/CF ratio calculated at 7 hr after CF administration. Plasma TB+PX+TP/CF ratios were statistically different (P<0.05) among breeds (MK; 0.155 ± 0.062, AK; 0.468 ± 0.107, AM; 0.254 ± 0.099). These results suggest that the pattern of drug biotransformation should be consistently tested on all the intra-species (inter-breeds). Further studies are exacted to determine the biochemical and molecular events underlying such an effect.
