Pharmacokinetics of cyclosporine pre- and post-liver transplantation.
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.
Hebert
Mary F
MF
University of Washington, Department of Pharmacy, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630, USA.
Wacher
Vincent J
VJ
Roberts
John P
JP
Benet
Leslie Z
LZ
D000328:Adult; D000437:Alcoholism / Q000150:complications; D015209:Cholangitis, Sclerosing / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006509:Hepatitis B / Q000378:metabolism; D006526:Hepatitis C / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period
D007166:Immunosuppressive Agents; D016572:Cyclosporine