METABOLIC CAGE ISOLATION REDUCES ANTIPYRINE CLEARANCE IN RATS

Rats are commonly isolated individually in cages during pharmacokinetic studies. However, isolation-induced changes in drug disposition are not commonly examined. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of the study was to investigate the effect of individual housing on antipyrine pharmacokinetics. Rats were individually housed in either standard polycarbonate boxes (n = 8) or metabolic cages (n = 10). On day 1 and day 9 rats were administered a single intravenous bolus injection of antipyrine 20 mg kg(-1). Blood samples (100 mu L) were obtained before and at 20, 40, 60, 90, 120, 180, 240, 300 and 360 min following the administration of the dose. Rats remained in their respective cages between evaluations. Serum antipyrine concentrations were determined by capillary electrophoresis. Pharmacokinetic parameters were estimated by model-independent methods. Antipyrine clearance was reduced by 38.4% in rats isolated in metabolic cages for eight days (P = 0.013) while the volume of distribution remained unchanged in both rat groups. These data suggest that the isolation of rats in metabolic cage systems may markedly alter the pharmacokinetics of xenobiotics, thus possibly masking experimental outcome.