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Decreased tacrolimus levels after administration of rifampin to a patient with renal transplant.

The calcineurin inhibitor tacrolimus is used to prevent organ rejection following renal transplant. This drug is metabolized through the hepatic cytochrome P450 (CYP450) 3A enzymes, in particular, CYP3A4 and CYP3A5. A strong relationship between CYP3A5 genetic polymorphisms and the pharmacokinetics of tacrolimus has been demonstrated in kidney, heart, and liver graft recipients. Previous studies have shown that carriers of the CYP3A5*1 allele require larger doses of tacrolimus to achieve target blood concentrations than patients with other alleles. The frequency of this allele varies depending on ethnicity and is more common among Asian and African American people than among whites. Rifampin is known to affect the metabolism of tacrolimus through induction of CYP3A4 and, to a far lesser extent, CYP3A5. Although the interaction between these drugs is in theory well recognized, its clinical significance in adults has been reported for only 4 Asian patients, 2 Hispanic patients, and one Kuwaiti patient. To our knowledge, this interaction has not been described previously for adult white patients, the population with the lowest frequency of CYP3A5*1 allele carriers. Here, we describe a white patient who had undergone a renal transplant and who experienced a clinically significant interaction between tacrolimus and rifampin.