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The P-gp/MDR1 multidrug transporter mediates detoxification of numerous drugs, including colchicine, and CYP3A4 is key to the biotransformation of colchicine. We investigated the effects of CYP3A4 and P-gp/MDR1 polymorphisms on bioavailability of colchicine in patients with Familial Mediterranean fever (FMF). Forty-eight Turkish patients with FMF treated with colchicine were genotyped for 3435C&gt;T, (-)1A&gt;G, 61A&gt;G, 1199G&gt;A, 1236C&gt;T, 2677G&gt;A, 2677G&gt;T polymorphisms in the P-gp/MDR1 gene and 3435C&gt;T, 1B(-392A&gt;G), 2(15713T&gt;C), 3(23171T&gt;C), 12(21896C&gt;T), 17(15615T&gt;C) polymorphisms in the CYP3A4 gene. Doses of colchicine administered to patients did not differ with respect to P-gp/MDR1 or CYP3A4 gene polymorphism. We also determined the genotype distributions of CYP3A4 and P-gp/MDR1 genes among FMF patients. There was no significant gender difference in the P-gp/MDR1 polymorphism, whereas there were significant gender differences in the frequencies of 15713T&gt;C and 15615T&gt;C polymorphisms in the CYP3A4 gene. No significant relationship was found between colchicine doses that would introduce optimal clinical response and affect the therapeutic dose and CYP3A4 and P-gp/MDR1 gene polymorphisms in these FMF patients.

Lack of an effect of CYP3A4 and MDR1 gene polymorphisms on colchicine pharmacogenetics in the treatment of Familial Mediterranean fever