Inter-individual difference determinant of prednisolone pharmacokinetics for Japanese renal transplant recipients in the maintenance stage.

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Miura M, Inoue K, Kagaya H, Saito M, Habuchi T, Satoh S

Inter-individual difference determinant of prednisolone pharmacokinetics for Japanese renal transplant recipients in the maintenance stage.

Xenobiotica. 2009 Dec;39(12):939-45. doi: 10.3109/00498250903294361.

PubMed ID

19795924 [ View in PubMed

]

Abstract

The objective of this study was to elucidate the effects of CYP3A5, ABCB1, NR1I2 and NR3C1 BclI gene polymorphisms on prednisolone exposure for 65 Japanese renal transplant recipients in the maintenance stage one year after transplantation. Prednisolone dosage ranged from 2.5 to 15.0 mg day(-1) based on individual immunosuppressive states. The dose-adjusted area under the plasma concentration-time curve (AUC(0-24)) and the maximal plasma concentration (C(max)) of prednisolone in recipients with the BclI G allele were significantly higher than in those with the CC genotype (p = 0.029 and 0.021, respectively), but there were no significant differences in the half-life and T(max) of prednisolone between the two groups. None of the CYP3A5, ABCB1 or NR1I2 allele variants had any significant influence on the dose-adjusted AUC(0-24) of prednisolone. The NR3C1 BclI polymorphism was important in the inter-individual variability of prednisolone pharmacokinetics. The transactivation of the CYP3A4 promoter by prednisolone via the glucocorticoid receptor might be especially responsive for intestinal CYP3A4.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Prednisone	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inducer	Details