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PHARMACOKINETICS AND PHARMACODYNAMICS

Pharmacokinetics of Cyclosporine Pre- and Post-Liver Transplantation

Mary F. Hebert, PharmD, Vincent J. Wacher, PhD, John P. Roberts, MD and Leslie Z. Benet, PhD

From the Department of Pharmacy, University of Washington, Seattle (Dr. Hebert) and the Department of Biopharmaceutical Sciences (Dr. Wacher, Dr. Benet) and Department of Transplantation (Dr. Roberts), University of California, San Francisco. Dr. Wacher's current affiliation is Ontogen Corporation, Carlsbad, California.

Cyclosporine (CyA) is an immunosuppressant metabolized primarily by the liver and small intestine. The pharmacokinetics (PK) of CyA were studied in 6 patients prior to and 1 to 3 months after liver transplantation (tx). Sixteen blood samples were collected over 24 hours following a 2-3 mg/kg intravenous dose of CyA. PK parameters, presented as mean SD, were estimated using noncompartmental techniques. Pre-tx AUCs (14,540 ± 5200 µg•h/L) were found to be significantly higher than during the post-tx phase (8120 ± 2870 µg•h/L, p = 0.04). CyA clearance values were lower pre-tx as compared to post-tx (0.21 ± 0.06 L/h/kg vs. 0.38 ± 0.14 L/h/kg, respectively). There was no change in volume of distribution. End-stage liver disease can markedly decrease hepatic clearance of CyA relative to patients with stable hepatic function post-liver tx. The degree of impairment in clearance is not consistent or predictable based on liver function tests.

Address for reprints: Mary F. Hebert, PharmD, Associate Professor, University of Washington, Department of Pharmacy, H- 375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630.


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