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  • Title: Pharmacokinetics of cyclosporine pre- and post-liver transplantation.
    Author: Hebert MF, Wacher VJ, Roberts JP, Benet LZ.
    Journal: J Clin Pharmacol; 2003 Jan; 43(1):38-42. PubMed ID: 12520626.
    Abstract:
    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 micrograms.h/L) were found to be significantly higher than during the post-tx phase (8120 +/- 2870 micrograms.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.
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