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The CYP3A5* 3 and CYP3A4* 1B alleles have been related with tacrolimus (Tac) dose requirements. The rare CYP3A4* 22 variant has also been associated with a significantly lower Tac dose. We genotyped the three single-nucleotide polymorphisms in 206 kidney-transplanted patients who received Tac as the primary immunosuppressor. CYP3A5* 1 and CYP3A4* 1B allele carriers received a significantly higher Tac dose (P< 0.01) compared with wild-type homozygotes. We did not find significant differences between the CYP3A4* 22 genotypes, either nominally or according to the CYP3A5 genotype (expressers vs. nonexpressers). Sequencing of CYP3A4 coding exons in a total of 15 patients revealed only one nonreported missense change (p. P227> T) in one patient. We concluded that CYP3A5* 3 and CYP3A4* 1B were the main determinants of the Tac dose-adjusted blood concentration in our cohort of renal …