Effects of CYP2C93 and 13 alleles on the pharmacokinetics and pharmacodynamics of glipizide in healthy Korean subjects

Glipizide is a second-generation sulfonylurea antidiabetic drug. It is principally metabolized to inactive metabolites by genetically polymorphic CYP2C9 enzyme. In this study, we investigated the effects of CYP2C9*3 and *13 variant alleles on the pharmacokinetics and pharmacodynamics of glipizide. T...

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Vydané v:Archives of pharmacal research Ročník 45; číslo 2; s. 114 - 121
Hlavní autori: Kim, Nam-Tae, Cho, Chang‑Keun, Kang, Pureum, Park, Hye-Jung, Lee, Yun Jeong, Bae, Jung‑Woo, Jang, Choon-Gon, Lee, Seok-Yong
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Seoul Pharmaceutical Society of Korea 01.02.2022
대한약학회
Predmet:
Administration, Oral
Adult
Alleles
Asians
blood glucose
Blood Glucose - metabolism
Cytochrome P-450 CYP2C9 - genetics
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - genetics
enzymes
Female
Genetic Predisposition to Disease
genotype
glipizide
Glipizide - blood
Glipizide - pharmacokinetics
Glipizide - pharmacology
Healthy Volunteers
Humans
hypoglycemic agents
Hypoglycemic Agents - blood
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - pharmacology
insulin
Male
Medicine
metabolites
oral administration
pharmacodynamics
pharmacokinetics
Pharmacology/Toxicology
Pharmacy
Polymorphism, Genetic - drug effects
Republic of Korea
Research Article
Young Adult
약학
Republic of Korea
CYP2C9
Genotype
Pharmacodynamics
Glipizide
Pharmacokinetics
Genetic polymorphism
ISSN:0253-6269, 1976-3786, 1976-3786
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Popis
Shrnutí:Glipizide is a second-generation sulfonylurea antidiabetic drug. It is principally metabolized to inactive metabolites by genetically polymorphic CYP2C9 enzyme. In this study, we investigated the effects of CYP2C9*3 and *13 variant alleles on the pharmacokinetics and pharmacodynamics of glipizide. Twenty-four healthy Korean volunteers (11 subjects with CYP2C9*1/*1 , 8 subjects with CYP2C9*1/*3 , and 5 subjects with CYP2C9*1/*13 ) were recruited for this study. They were administered a single oral dose of glipizide 5 mg. The plasma concentration of glipizide was quantified for pharmacokinetic analysis and plasma glucose and insulin concentrations were measured as pharmacodynamic parameters. The results represented that CYP2C9*3 and *13 alleles significantly affected the pharmacokinetics of glipizide. In subjects with CYP2C9*1/*3 and CYP2C9*1/*13 genotypes, the mean AUC 0–∞ were increased by 44.8% and 58.2%, respectively (both P  < 0.001), compared to those of subjects with CYP2C9*1/*1 genotype, while effects of glipizide on plasma glucose and insulin levels were not significantly different between CYP2C9 genotype groups. In conclusion, individuals carrying the defective CYP2C9*3 and CYP2C9*13 alleles have markedly elevated plasma concentrations of glipizide compared with CYP2C9*1/*1 wild-type.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
https://doi.org/10.1007/s12272-021-01366-y
ISSN:0253-6269
1976-3786
1976-3786
DOI:10.1007/s12272-021-01366-y