Tacrolimus/cerivastatin interaction study in liver transplant recipientsUniversity Department of Medicine, Addenbrooke's NHS Trust, Cambridge, UK Dr Wolfgang M ck, Institute of Clinical Pharmacology, Bayer AG, Pharma Research Center, Aprather Weg, Building 470, D-42096 Wuppertal, Germany. Tel.: + 49 202 36 8795; Fax: + 49 202 36 8180; E-mail: With advances in immunosuppressive treatment, graft loss due to acute and chronic rejection has declined such that a variety of metabolic disturbances are now assuming increasing importance in long-term survival of liver transplant patients. Accelerated atherosclerosis has thus become a crucial factor in patient survival after liver transplantation [1], and lipid-lowering drug therapy with 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors has significant potential to alleviate cardiovascular complications in those patients [2 4].The HMG-CoA reductase inhibitor cerivastatin has several pharmacokinetic characteristics rendering it rather insensitive to drug interactions, e.g. complete absorption ( 98%), high bioavailability (60%) due to moderate first-pass extraction, dual metabolic pathway (demethylation: metabolite M-1; hydroxylation: M-23), short plasma elimination half-life of 2 3 h, and biliary (70%) and renal (30%) route of elimination of the formed metabolites [9]. Regarding CYP-mediated metabolic clearance, cerivastatin shows high affinity to CYP 2C8, which catalyses the formation of metabolites M-1 and M-23 almost to the same extent. affinity for CYP 3A4 is considerably lower; CYP 3A4 contributes only to the formation of M-1. Nonspecific or specific CYP 3A4 inhibitors such as cimetidine, erythromycin, itraconazole, and mibefradil do not show clinically relevant interactions with cerivastatin [10]. Nevertheless, single and multiple dosing of once-daily 0.
