Cyclosporine, a cyclic polypeptide with potent immunosuppressive properties, 1 has been successfully used to prevent the rejection of transplanted organs such as kidneys, livers, hearts, and bone marrow. 2–5 It is highly lipophilic and is eliminated primarily by metabolism in the liver. 6 Recent studies in transplant patients indicate cyclosporine to be a low-to-intermediate clearance drug. We had a unique opportunity to directly determine the hepatic extraction ratio of this drug in a pediatric liver transplant recipient. The patient was a 4-year-old male who underwent liver transplantation for α1-antitrypsin deficiency. Subsequent to his first transplantation, he progressed well until 1 month following surgery when he developed hepatic artery thrombosis. He received a second liver 53 d after the first transplant. On the day prior to the second transplant, the liver function tests were as follows: alkaline phosphatase, 63 IU/L; serum glutamic oxaloacetic transaminase (SGOT), 654 IU/L; serum glutamic pyruvic transamine (SGPT), 273 IU/L; bilirubin (total), 1.0 mg/dL; bilirubin (direct), 0.2 mg/dL. This indicated that the patient did not have a normally functioning liver. The patient did not receive any drugs known to induce or inhibit the drug-metabolizing enzyme systems of the liver at any time prior to the second transplant. At the time of the study, the patient received cyclosporine and a low dose of prednisolone as immunosuppressants, captopril for the treatment of hypertension, and systemic antibiotics. Prior to the operation, 30 mg im of secobarbital was administered. Just prior to the removal of the first transplanted liver, simultaneous blood samples were obtained from the hepatic and portal veins. Blood samples were kept frozen until analyzed for whole blood cyclosporine concentration by HPLC. The blood was extracted using the procedure of Sawchuck and Cartier. 7 Samples were analyzed using a 5-μm C18 , column (Supelco, Bellefonte, PA) heated to 70°C and UV detection (model 441; Waters Associates, Milford, MA) at 214 nm. Standards were prepared in blank blood, and the internal standard was cyclosporine D (Sandoz Pharmaceuticals, Basel, Switzerland). The mobile phase was 68% acetonitrile, delivered at 1.8 mL/min. Under these conditions, the retention time for cyc1osporine was 9.8 min and that for cyclosporine D was 12.8 min. The CV of the analytical method was 3.95% at 600 ng/mL (n = 10). The concentration of cyc1osporine in the portal vein (PV) was 596 ng/mL, whereas the hepatic vein (HV) concentration was 500 ng/mL. The hepatic extraction ratio was: In this patient, the first transplanted liver was 740 g in weight. The hepatic blood flow in humans is 100 mL/100 g of liver weight. 8 Therefore, based on an estimated blood flow of