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• W2000576945 abstract "Objectives: The aims of this study were to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant recipients, to use this model to compare cytochrome P450 3A5 (CYP3A5) genotype–based initial dosing of tacrolimus with standard per-kilogram–based dosing, and to predict the best starting dose of tacrolimus based on patient genotype to achieve a trough concentration between 6 and 10 µg/L by day 5 posttransplantation. Methods: Population analysis was performed using the software program NONMEM. Tacrolimus dosing regimens were compared by predicting tacrolimus trough concentrations in a simulated data set by running NONMEM with population parameters fixed at the final model estimates. Data from 173 patients with 1554 tacrolimus concentration–time measurements were modeled. Results: Tacrolimus disposition was well described by a 2-compartment model with first-order elimination and first-order absorption after a lag time. Patient CYP3A5 genotype (rs776746), weight, hematocrit, and postoperative day were identified as significant covariates effecting tacrolimus apparent oral clearance (CL/F), with higher CL/F in CYP3A5*1 allele carriers, heavier patients, patients with low hematocrit, and in the immediate posttransplantation period. Typical population estimates for tacrolimus CL/F in CYP3A5*1 allele carriers and noncarriers were 40.8 and 25.5 L/h, respectively. Conclusions: In patients carrying the CYP3A5*1 allele, a per-kilogram dose of 0.075 mg/kg twice daily seemed too much low with approximately 65% of simulated subjects predicted to achieve a trough below 6 µg/L at day 5 posttransplantation. To reduce the risk of under immunosuppression in the immediate posttransplantation period, carriers of a CYP3A5*1 allele are likely to benefit from a tacrolimus starting dose of either 10 mg or 0.115 mg/kg twice daily." @default.
• W2000576945 created "2016-06-24" @default.
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• W2000576945 date "2014-02-01" @default.
• W2000576945 modified "2023-09-27" @default.
• W2000576945 title "Population Pharmacokinetics of Tacrolimus in Adult Kidney Transplant Patients" @default.
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• W2000576945 doi "https://doi.org/10.1097/ftd.0b013e31829f1ab8" @default.
• W2000576945 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24089074" @default.
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