Janus K, Antoszek J, Suszycki S
Department of Physiological Chemistry, University of Agriculture, ul. Doktora Judyma 26, 71-466 Szczecin, Poland.
Res Vet Sci. 2001 Apr;70(2):109-13. doi: 10.1053/rvsc.2000.0446.
The aim of this study was to determine the effect of short-term starvation or water deprivation on the pharmacokinetics of caffeine in calves. The experiment was carried out on 30 Holstein-Friesian calves (10 calves in a control group, 10 calves in a 'starved' group and 10 calves in a 'water-deprived' group) aged 24-25 days. Control group calves were given caffeine at 24-25 and 28-29 days of age. In the experimental groups caffeine studies were performed before and after 4 days of starvation or water deprivation. In the control group no significant differences between the pharmacokinetic parameters of caffeine in 24-25 and 28-29 day-old calves were observed. Starvation for 4 days was associated with an increase in the mean residence time (MRT) of caffeine in each subject. The increase was statistically significant (P < 0.01). After starvation the total plasma clearance of caffeine decreased (about 20 per cent). The decrease was statistically significant (P < 0.05). The volume of caffeine distribution (V(ss)) was slightly but not significantly increased. Similarly, water deprivation was associated with significant increase in the mean residence time of caffeine in each subject. The total plasma clearance of caffeine decreased (about 30 per cent). This decrease was statistically significant (P < 0.01). The volume of caffeine distribution was slightly but not significantly decreased. Results obtained in this study indicate that short-term (for 4 days) starvation or water deprivation leads to a general inhibition of hepatic P450 enzymatic system and may impair the elimination of drugs that undergo metabolism by these enzymes.
本研究的目的是确定短期饥饿或缺水对犊牛体内咖啡因药代动力学的影响。实验在30头24 - 25日龄的荷斯坦 - 弗里生犊牛上进行（10头犊牛为对照组，10头犊牛为“饥饿”组，10头犊牛为“缺水”组）。对照组犊牛在24 - 25日龄和28 - 29日龄时给予咖啡因。在实验组中，在饥饿或缺水4天前后进行咖啡因研究。在对照组中，未观察到24 - 25日龄和28 - 29日龄犊牛咖啡因药代动力学参数之间的显著差异。饥饿4天与每个受试者体内咖啡因的平均驻留时间（MRT）增加有关。这种增加具有统计学意义（P < 0.01）。饥饿后咖啡因的总血浆清除率降低（约20%）。这种降低具有统计学意义（P < 0.05）。咖啡因分布容积（V(ss)）略有增加，但无统计学意义。同样，缺水与每个受试者体内咖啡因的平均驻留时间显著增加有关。咖啡因的总血浆清除率降低（约30%）。这种降低具有统计学意义（P < 0.01）。咖啡因分布容积略有降低，但无统计学意义。本研究获得的结果表明，短期（4天）饥饿或缺水会导致肝脏P450酶系统普遍受到抑制，并可能损害通过这些酶进行代谢的药物的消除。
