Tacrolimus Population Pharmacokinetics and Multiple CYP3A5 Genotypes in Black and White Renal Transplant Recipients

Journal of Clinical Pharmacology
Olivia CampagneKathleen M Tornatore

Abstract

Tacrolimus exhibits inter-patient pharmacokinetic variability attributed to CYP3A5 isoenzymes and the efflux transporter, P-glycoprotein. Most black renal transplant recipients require higher tacrolimus doses compared to whites to achieve similar troughs when race-adjusted recommendations are used. An established guideline provides tacrolimus genotype dosing recommendations based on CYP3A5*1(W/T) and loss of protein function variants: CYP3A5*3 (rs776746), CYP3A5*6 (rs10264272), CYP3A5*7 (rs41303343) and may provide more comprehensive race-adjusted dosing recommendations. Our objective was to develop a tacrolimus population pharmacokinetic model evaluating demographic, clinical, and genomic factors in stable black and white renal transplant recipients. A secondary objective investigated race-based tacrolimus regimens and genotype-specific dosing. Sixty-seven recipients receiving oral tacrolimus and mycophenolic acid ≥6 months completed a 12-hour pharmacokinetic study. CYP3A5*3,*6,*7 and ABCB1 1236C>T, 2677G>T/A, 3435C>T polymorphisms were characterized. Patients were classified as extensive, intermediate, and poor metabolizers using a novel CYP3A5*3*6*7 metabolic composite. Modeling and simulation was performed with computer sof...Continue Reading

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Citations

Nov 11, 2018·British Journal of Clinical Pharmacology·Olivia CampagneKathleen M Tornatore
Apr 7, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Moataz E MohamedUNKNOWN DeKAF Genomics and GEN03 Investigators
Feb 25, 2020·Therapeutic Drug Monitoring·Takaaki YamadaSatohiro Masuda
Jul 30, 2020·Expert Opinion on Drug Metabolism & Toxicology·Alexandra L DegraeveLaure Elens
May 8, 2019·Journal of Clinical Pharmacology·Calvin J MeaneyKathleen M Tornatore
Aug 13, 2020·Clinical Pharmacokinetics·Ranita KirubakaranJane E Carland
Jan 27, 2021·International Journal of Molecular Sciences·Song GaoDong Liang
Apr 1, 2021·British Journal of Clinical Pharmacology·Lisa C MartialDirk Jan A R Moes
Jun 14, 2021·Drug Discovery Today·Tom C ZwartDirk Jan A R Moes
Sep 25, 2021·British Journal of Clinical Pharmacology·Ranita KirubakaranSophie L Stocker
Jun 15, 2021·Therapeutic Drug Monitoring·Ranita KirubakaranJane E Carland

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