J Clin Pharmacol
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DRUG METABOLISM

Effect of Age and Postoperative Time on Cytochrome P450 Enzyme Activity Following Liver Transplantation

Shanshan Liu, MD, Reginald F. Frye, PharmD, PhD, Robert A. Branch, MD, Raman Venkataramanan, PhD, FCP, John J. Fung, MD, PhD and Gilbert J. Burckart, PharmD, FCP

From the School of Pharmacy, University of Southern California, Los Angele (Dr Liu, Dr Burckart); the Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville (Dr Frye); and the Center for Clinical Pharmacology (Dr Branch), Department of Pharmaceutical Science (Dr Venkataramanan), and the Thomas E. Starzl Transplantation Institute (Dr Fung), University of Pittsburgh, Pennsylvania. Supported by grant DK34475 from the National Institutes of Health (NIH) and grant 5M01 RR00056 from the National Center for Research Resources/General Clinical Research Centers, NIH.

This study evaluates the changes in cytochrome P450 (CYP) enzyme activity in orthotopic liver transplant (OLTx) patients in relation to recipient age and postoperative time. Thirty-eight stable OLTx patients, separated into younger and older age groups, and 21 healthy subjects were given a 5-drug cocktail including chlorzoxazone (CYP2E1), caffeine (CYP1A2), dapsone (CYP3A4), mephenytoin (CYP2C19), and debrisoquin (CYP2D6). The phenotypic indexes were determined for each associated enzyme. Compared to young healthy subjects, the CYP2E1 capacity was significantly increased in younger and older OLTx patients (P < .001), while the CYP2C19 capacity was decreased significantly in younger and older OLTx patients within 30 days postoperatively (P < .01). The CYP2D6 capacity was significantly lower after 30 days postoperatively in older OLTx patients (P < .05). The authors conclude that within 30 days postoperatively, CYP2E1 capacity was markedly elevated in OLTx patients, while 2C19 function was significantly reduced. CYP2D6 capacity was impaired after 30 days postoperatively. Younger and older OLTx patients experienced similar changes in major CYP450 enzyme capacity following liver transplantation.

Key Words: Cytochrome P450 • liver transplantation • phenotype • age

Address for reprints: Gilbert J. Burckart, University of Southern California, School of Pharmacy, 1985 Zonal Ave, PSC 100, Los Angeles, CA 90033.






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