Mechanisms of Clinically Relevant Drug Interactions Associated with Tacrolimus
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Clin Pharmacokinet 2002; 41 (11): 813-851 0312-5963/02/0011-0813/$25.00/0 © Adis International Limited. All rights reserved.
Mechanisms of Clinically Relevant Drug Interactions Associated with Tacrolimus Uwe Christians,1,2 Wolfgang Jacobsen,1 Leslie Z. Benet 3 and Alfonso Lampen 4 1 Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado, USA 2 Institut für Pharmakologie, Medizinische Hochschule Hannover, Hannover, Germany 3 Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, California, USA 4 Department of Food Toxicology, School of Veterinary Medicine, Hannover, Germany
Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Pharmacokinetics of Tacrolimus . . . . . . . . . . . . . . . . . . . . . . 2. Pharmacokinetic Drug Interactions . . . . . . . . . . . . . . . . . . . . 2.1 Effects of Other Drugs on Tacrolimus Pharmacokinetics . . . . . . 2.1.1 Inhibition of Drug Metabolism . . . . . . . . . . . . . . . . . . 2.1.2 Induction of Drug Metabolism . . . . . . . . . . . . . . . . . 2.1.3 Role of the Small Intestine . . . . . . . . . . . . . . . . . . . . 2.1.4 Potential Role of P-Glycoprotein . . . . . . . . . . . . . . . . 2.2 Effect of Tacrolimus on Pharmacokinetics of Other Drugs . . . . . 2.2.1 Inhibition of Drug Metabolism and P-Glycoprotein . . . . . 2.2.2 Induction of Drug Metabolism and P-Glycoprotein . . . . . 2.3 Interactions in Patient Subpopulations . . . . . . . . . . . . . . . . 2.3.1 Gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.2 Ethnicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.3 Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Poorly Understood But Potentially Clinically Relevant Interactions 2.4.1 Mycophenolate Mofetil . . . . . . . . . . . . . . . . . . . . . 2.4.2 Sirolimus and Everolimus . . . . . . . . . . . . . . . . . . . . . 2.4.3 Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.4 HMG-CoA Reductase Inhibitors . . . . . . . . . . . . . . . . 2.4.5 HIV Protease Inhibitors . . . . . . . . . . . . . . . . . . . . . . 2.4.6 Psychiatric Drugs . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.7 Herb and Food Components . . . . . . . . . . . . . . . . . . 3. Intentional Drug Interactions . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Increase of Oral Bioavailability . . . . . . . . . . . . . . . . . . . . 3.2 Multidrug Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Pharmacodynamic Drug Interactions . . . . . . . . . . . . . . . . . . . 5. Clinical Management of Interactions with Tacrolimus . . . . . . . . .
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