-Original-

Effectiveness of Measuring Genetic Polymorphisms in Metabolizing Enzymes of Tacrolimus within One Medical Facility

Tomohiro Kaneko¹, Momoko Arai¹, Atsushi Watanabe² and Shuichi Tsuruoka³

¹Divisions of Nephrology, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan
²Division of Personalized Genetic Medicine, Nippon Medical School Hospital, Tokyo, Japan
³Divisions of Nephrology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan

Objectives: Because genetic polymorphisms cause diverse activity in drug metabolizing enzymes, drug concentrations in the blood may be variable among patients. We analyzed the genotypes of CYP3A5 and MDR1, and investigated their relationship with whole blood drug concentrations.
Methods: Eight patients were administered an oral dose of tacrolimus for one week or longer prior to enrollment in this study. Whole blood concentrations for tacrolimus were measured 12 hours post oral administration, on the same day as genotyping, within our hospital using a fully automated gene analyzer. The procedures became so rapid that collection of blood samples could be completed within the same day (approximately one hour).
Results: The genotype frequency of CYP3A5 was ^*3/^*3 in five patients, ^*1/^*3 in two patients, and ^*1/^*1 in one patient. All five patients with ^*3/^*3 showed favorable increases in tacrolimus blood concentrations. In the two patients with ^*1/^*3, an increase in tacrolimus blood concentration was not readily achieved in one patient, but increased favorably in the other patient. In the patient with ^*1/^*1, tacrolimus was not detectable in the patient's blood. A favorable treatment effect was obtained by changing tacrolimus to cyclosporine. It is notable that genotypes in patients where tacrolimus was not detected in the blood were wild types: 2677G/G and 3435C/C in MDR1.
Conclusions: The measurement of genetic polymorphisms in metabolizing enzymes of tacrolimus, within one medical facility, is applicable for the selection of immunosuppressants and individual dosing for the treatment of autoimmune disease.

J Nippon Med Sch 2017; 84: 274-279

Keywords
tacrolimus, genetic polymorphism, CYP3A5, MDR1

Correspondence to
Tomohiro Kaneko, MD, PhD, Divisions of Nephrology, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo 206-8512, Japan
tomohiro@nms.ac.jp

Received, August 2, 2017
Accepted, October 30, 2017