Azole antifungals and inter-individual differences in drug metabolism: the role of pharmacogenomics and precision medicine

Biswas, Mohitosh; Shobana, John; Jinda, Pimonpan; Sukasem, Chonlaphat

doi:10.1080/17425255.2023.2203860

Cited by 2 publications

(1 citation statement)

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“…6,7 This encompassing enzymatic responsibility extends to an array of pharmaceuticals, including certain antifungal agents, antidepressants, proton pump inhibitors, and antiplatelet aggregation medications. [8][9][10][11] The CYP2C19 enzyme, owing to its intricate genetic diversity, has emerged as a focal point in pharmacogenomic investigations, wherein these genetic variances may conceivably modulate enzyme functionality and drug metabolism. 12 Notably, the CYP2C19 allele denoted as CYP2C19*17, endowed with an augmenting influence on enzyme activity, might necessitate a commensurate escalation in drug dosages to attain therapeutic outcomes.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of CYP2C19 Genetic Variant and Its Lack of Association with Valproic Acid Plasma Concentrations Among Zhuang and Han Schizophrenia Patients in Guangxi

Teng,

Qin,

et al. 2024

PGPM

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Purpose To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations. Patients and Methods Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 *1, *2, and *3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression. Results The study identified five CYP2C19 genotypes at the *2 and *3 loci, with the *3/*3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18–60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age. Conclusion In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.

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