Effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy subjects

Kang, Pureum; Cho, Chang‐Keun; Jang, Choon‐Gon; Lee, Seok-Yong; Lee, Yun Jeong; Choi, Chang‐Ik; Bae, Jung‐Woo

doi:10.1007/s12272-023-01448-z

Arch. Pharm. Res.

2023

DOI: 10.1007/s12272-023-01448-z

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Effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy subjects

Pureum Kang

Chang‐Keun Cho

Choon‐Gon Jang

et al.

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Cited by 6 publications

References 48 publications

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Meta‐Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure

Fostvedt,

Liu,

Wang

et al. 2024

Clinical Pharm in Drug Dev

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Abrocitinib is a selective Janus kinase 1 inhibitor approved for the treatment of atopic dermatitis. It is metabolized primarily by cytochrome P450 (CYP) 2C19 (approximately 53%) and CYP2C9 (approximately 30%), which form 2 active metabolites. The pharmacologic activity of abrocitinib is attributable to the unbound exposures of abrocitinib and those metabolites with active moiety area under the plasma concentration–time curve (AUC) considered the best measure of the total pharmacological effect. The effect of CYP2C19 and/or CYP2C9 genotypes on abrocitinib and active moiety exposures were evaluated using a meta‐analysis of the noncompartmental estimates of exposure pooled from 10 clinical studies. A linear mixed‐effects model was developed on the basis of the power model to evaluate the effect of CYP2C19 and/or CYP2C9 genotypes on exposure (i.e., abrocitinib AUC and peak plasma concentration, active moiety AUC and peak plasma concentration). The genotypes were evaluated individually and as a combined phenotype effect. When evaluating the poor metabolizers of CYP2C19 or CYP2C9 individually, the estimated increases were 44.9% and 42.0% in active moiety AUC, respectively. The combined phenotype models showed a 0.6% decrease, and 25.1% and 10.5% increases in the active moiety AUC for “elevated,” “mixed,” and “reduced” metabolizers, respectively. Overall, the active moiety exposures did not appear to be affected to a clinically meaningful extent by different genotypes of CYP2C19 and/or CYP2C9.

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Meta‐Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure

Fostvedt,

Liu,

Wang

et al. 2024

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

show abstract

Effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on the pharmacokinetics of tolperisone

Byeon,

Cho,

Kang

et al. 2023

Arch. Pharm. Res.

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Physiologically based pharmacokinetic (PBPK) modeling to predict the pharmacokinetics of irbesartan in different CYP2C9 genotypes

Cho,

Kang,

Jang

et al. 2023

Arch. Pharm. Res.

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Effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of gliclazide in healthy subjects

Cited by 6 publications

References 48 publications

Meta‐Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure

Meta‐Analysis of Noncompartmental Pharmacokinetic Parameters to Evaluate the Impact of CYP2C19 and CYP2C9 Genetic Polymorphisms on Abrocitinib Exposure

Effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on the pharmacokinetics of tolperisone

Physiologically based pharmacokinetic (PBPK) modeling to predict the pharmacokinetics of irbesartan in different CYP2C9 genotypes

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