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Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans

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Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans

dc.contributor.author	Reyes-González, Stephanie
dc.contributor.author	Barreras, Camila de las
dc.contributor.author	Reynaldo, Gledys
dc.contributor.author	Rodríguez-Vera, Leyanis
dc.contributor.author	Vlaar, Cornelis
dc.contributor.author	Lopez Mejias, Vilmali
dc.contributor.author	Monbaliu, Jean-Christophe M.
dc.contributor.author	Stelzer, Torsten
dc.contributor.author	Mangas Sanjuan, Victor
dc.contributor.author	Duconge,Jorge
dc.date.accessioned	2020-12-23T13:31:32Z
dc.date.available	2021-08-19T04:45:04Z
dc.date.issued	2020
dc.identifier.citation	Reyes-González, Stephanie Barreras, Camila de las Reynaldo, Gledys Rodríguez-Vera, Leyanis Vlaar, Cornelis Lopez Mejias, Vilmali Monbaliu, Jean-Christophe M. Stelzer, Torsten Mangas Sanjuan, Victor Duconge,Jorge 2020 Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans Drug Metabolism and Personalized Therapy 1 7
dc.identifier.uri	https://hdl.handle.net/10550/76782
dc.description.abstract	Objectives: The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods: Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The ke of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h−1. Ka and Vd parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. Results: In the carrier group (n=64), 53 subjects were single-carriers and 11 double-carriers (i.e., 2/2, 2/3, 2/5, 3/5, and 3/8). The mean peak concentration (Cmax) was higher for wild-type (0.36±0.12 vs. 0.32±0.14 mg/L). Likewise, the average clearance (CL) parameter was faster among non-carriers (0.22±0.03 vs. 0.17±0.05 L/h; p=0.0001), with also lower area under the curve (AUC) when compared to carriers (20.43±6.97 vs. 24.78±11.26 h mg/L; p=0.025). Statistical analysis revealed a significant difference between groups with regard to AUC and CL, but not for Cmax. This can be explained by the variation of ke across different genotypes. Conclusions: The results provided useful information for warfarin dosing predictions that take into consideration important individual PK and genotyping data.
dc.language.iso	eng
dc.relation.ispartof	Drug Metabolism and Personalized Therapy, 2020, p. 1-7
dc.subject	Farmàcia Investigació
dc.title	Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans
dc.type	journal article	es_ES
dc.date.updated	2020-12-23T13:31:32Z
dc.identifier.doi	10.1515/dmdi-2020-0135
dc.identifier.idgrec	142229
dc.rights.accessRights	open access	es_ES