title: Pharmacokinetics of a Once-Daily Dose of Tacrolimus Early After Liver Transplantation: With Special Reference to CYP3A5 and ABCB1 Single Nucleotide Polymorphisms.
abstract: BACKGROUND The aim of the present study was to investigate the pharmacokinetics of the once-daily tacrolimus formulation (QD form) in relation to polymorphisms of the donor cytochrome P450 family 3 sub-family A polypeptide 5 (CYP3A5) gene and recipient adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1) gene. MATERIAL AND METHODS A total of 80 consecutive living-donor liver transplant (LDLT) recipients were started on the QD form of tacrolimus (day 1), and 60 patients were completely followed for 7 days early after liver transplantation in order to evaluate the pharmacokinetics. RESULTS The concentration/dose (C/D) ratio in recipients with the donor CYP3A5 *1 allele was significantly lower throughout the observation period compared with those with the CYP3A5 genotype *3/*3 (p<0.001), while no effect of single-nucleotide polymorphisms (SNPs) of ABCB1 was observed. The administered doses required to achieve the target trough level were significantly higher on day 7 than on day 1 among all groups, regardless of the differences in the SNPs, especially among those with donor CYP3A5 *1 allele. The tacrolimus concentration was kept within the targeted level all through the study regardless of SNPs. CONCLUSIONS The donor CYP3A5 *1 allele correlated with the lower C/D ratio after administration of the QD form, and higher doses of QD-form tacrolimus and careful monitoring for the trough level should be considered, especially in recipients with the donor CYP3A5 *1 allele.
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Yoichi
authors: Y
authors: Miyata
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Nobuhisa
authors: N
authors: Akamatsu
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Yasuhiko
authors: Y
authors: Sugawara
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Junichi
authors: J
authors: Kaneko
authors: Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan.
authors: Takehito
authors: T
authors: Yamamoto
authors: Department of Pharmacy, The University of Tokyo Hospital, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Suzuki
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Junichi
authors: J
authors: Arita
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan, Tokyo, Japan.
authors: Yoshihiro
authors: Y
authors: Sakamoto
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Kiyoshi
authors: K
authors: Hasegawa
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Sumihito
authors: S
authors: Tamura
authors: Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Norihiro
authors: N
authors: Kokudo
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004334:Drug Administration Schedule; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus