CYP3A5 Genotype Markedly Influences the Pharmacokinetics of Tacrolimus and Sirolimus in Kidney Transplant Recipients

It is currently not clear whether the concentration‐time curves of the immunosuppressants differ with respect to the CYP3A5, MDR1, or MRP2 genotype in dose‐adapted stable kidney transplant patients. Dose/trough concentration ratios were obtained in 134 tacrolimus and 20 sirolimus‐treated patients, a...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2007-02, Vol.81 (2), p.228-234
Main Authors: Renders, L, Frisman, M, Ufer, M, Mosyagin, I, Haenisch, S, Ott, U, Caliebe, A, Dechant, M, Braun, F, Kunzendorf, U, Cascorbi, I
Format: Article
Language:English
Subjects:
Adult
Aged
Area Under Curve
Biological and medical sciences
Biological Availability
Calcium Channel Blockers - metabolism
Calcium Channel Blockers - pharmacokinetics
Calcium Channel Blockers - therapeutic use
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Drug Therapy, Combination
Female
Genetic Variation
Genotype
Half-Life
Humans
Immunosuppressive Agents - metabolism
Immunosuppressive Agents - pharmacokinetics
Immunosuppressive Agents - therapeutic use
Kidney Transplantation
Male
Medical sciences
Middle Aged
Mycophenolic Acid - analogs & derivatives
Mycophenolic Acid - metabolism
Mycophenolic Acid - pharmacokinetics
Mycophenolic Acid - therapeutic use
Pharmacology. Drug treatments
Prednisolone - metabolism
Prednisolone - pharmacokinetics
Prednisolone - therapeutic use
Sirolimus - metabolism
Sirolimus - pharmacokinetics
Sirolimus - therapeutic use
Tacrolimus - metabolism
Tacrolimus - pharmacokinetics
Tacrolimus - therapeutic use
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Summary:It is currently not clear whether the concentration‐time curves of the immunosuppressants differ with respect to the CYP3A5, MDR1, or MRP2 genotype in dose‐adapted stable kidney transplant patients. Dose/trough concentration ratios were obtained in 134 tacrolimus and 20 sirolimus‐treated patients, and plasma concentration‐time profiles were obtained from 16 (tacrolimus) and 10 (sirolimus) patients. Genotyping was carried out for CYP3A5 6986A>G; ABCB1 2677G>T/A, 3435C>T and ABCC2 −24C>T; 1249G>A; 3972C>T. Dose/trough concentration ratios were 0.67±0.3 and 1.36±0.73 × 103 l (P
ISSN:0009-9236
1532-6535
DOI:10.1038/sj.clpt.6100039