Dataset Information

Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

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 k e of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h-1. K a and V d 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 k e across different genotypes. Conclusions The results provided useful information for warfarin dosing predictions that take into consideration important individual PK and genotyping data.

SUBMITTER: Reyes-Gonzalez S

PROVIDER: S-EPMC7892629 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

Reyes-González Stephanie S de Las Barreras Camila C Reynaldo Gledys G Rodríguez-Vera Leyanis L Vlaar Cornelis C Mejias Vilmali Lopez VL Monbaliu Jean-Christophe M JM Stelzer Torsten T Mangas Victor V Duconge Jorge J

Drug metabolism and personalized therapy 20200819

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 k e of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h-1. K a and V d parameters were taken from literature. Data ...[more]

PMID: 32809952

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Project description:BackgroundLow vitamin D status, assessed using serum 25-hydroxyvitamin D [25(OH)D] concentration, has been associated with depression, but research among minority populations, such as Puerto Ricans is limited. We examined the association between serum 25(OH)D and self-reported depressive symptomatology across 3 waves of follow-up in a cohort of Puerto Rican adults residing in Massachusetts.ObjectivesWe evaluated the cross-sectional and longitudinal associations between serum 25(OH)D and self-reported depressive symptoms in the Boston Puerto Rican Health Study (BPRHS) cohort.MethodsParticipants of the BPRHS were evaluated for depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D). Serum 25(OH)D was measured at baseline (n = 1434), year 2 (n = 1218), and year 5 (n = 914). We categorized serum 25(OH)D concentration as sufficient (≥20 ng/mL), insufficient (12 to <20 ng/mL), and deficient (<12 ng/mL). Multivariable linear regression was used for cross-sectional analyses at baseline, and repeated measures mixed effects modeling was used over 3 waves of follow-up for longitudinal analyses. We conducted sensitivity analyses in vitamin D supplement nonusers and participants with complete data on baseline serum 25(OH)D and CES-D at all 3 visits.ResultsSerum 25(OH)D concentration was not associated with CES-D score in cross-sectional analysis [β = -0.85; 95% CI: -2.80, 1.10 for deficient compared with sufficient 25(OH)D; P-trend = 0.59] or in longitudinal analyses over 5 y [β = -0.41; 95% CI: -1.95, 1.13 for deficient compared with sufficient 25(OH)D; P-trend = 0.93]. Results were similar in sensitivity analyses restricted to vitamin D supplement nonusers (n = 1371) and in analyses conducted in participants with complete measures of baseline serum 25(OH)D and CES-D score at all 3 visits (n = 887) [β = -0.12; 95% CI: -1.98, 1.74 for deficient compared with sufficient 25(OH)D; P-trend = 0.93].ConclusionsWe did not observe a significant association between serum 25(OH)D and depressive symptomatology in the BPRHS cohort.

Dataset Information

Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

Publications

Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.

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