2022 年 47 巻 2 号 p. 71-75
This case involved a 27-year-old man with extreme obesity (body mass index 45.6 kg/m2) who had a history of fulminant hepatitis and living-donor liver transplantation at 11 years of age. He had been receiving oral sustained-release tacrolimus (TAC) 1.5 mg daily, and the trough concentration in the blood was below 2.0 ng/mL. He has an intrinsic cytochrome P450 3A5 (CYP3A5)*3/*3 (G/G) genotype and graft liver with CYP3A5*3 allele donated by his biological father. Additionally, there were no data on the phenotype of P-glycoprotein. He did not take medications, grapefruit, or St. John’s wort, which interact with CYP3A4 and P-glycoprotein. He intentionally took 30 mg of TAC and presented with symptoms of general malaise and poisoning. On the day of hospitalization (day 0), TAC was discontinued due to an elevated blood TAC concentration of > 60 ng/mL. Additionally, the blood TAC concentration exceeded 10 ng/mL for more than 3 days. He exhibited mild elevation of alanine aminotransferase, aspartate aminotransferase, and creatinine phosphokinase without apparent clinical symptoms. After discharge, blood TAC concentration decreased to 7.4 and 3.7 ng/mL on days 14 and 28, respectively, from the day of excessive TAC intake. Finally, the blood TAC concentration fell below 2.0 ng/mL on day 66. This case report showed that extreme obesity and the liver CYP3A5*3 allele delayed the elimination of TAC after excessive intake of the drug.
