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Effect of Pentobarbital Anaesthesia on Intestinal Absorption and Hepatic First‐pass Metabolism of Oxacillin in Rats, Evaluated by Portal‐Systemic Concentration Difference

The effects of anaesthesia on intestinal drug absorption and hepatic first‐pass metabolism in rats were investigated by observing the difference in the drug concentration between portal and systemic bloods. Oxacillin and pentobarbital were selected as a model drug and as an anaesthetic, respectively. Rats were divided into a conscious control group and an anaesthetized group. All rats were cannulated simultaneously in the portal vein and in the femoral artery, and oxacillin was orally administered after its intra‐arterial injection (double dosing). For the anaesthetized group, pentobarbital was intrasubcutaneously administered twice, first before intra‐arterial injection and again before oral administration of oxacillin. The arterial blood alone was sampled from the cannula in the femoral artery before oral administration, whereas the arterial and portal bloods were simultaneously sampled from both cannulated sites after oral administration. Oxacillin concentrations in plasma were assayed by HPLC.