Hypoglycemia and Glycemic Control With Glyburide in Women With Gestational Diabetes and Genetic Variants of Cytochrome P450 2C9 and/or OATP1B3.
Adult
Cytochrome P-450 CYP2C9
/ genetics
Diabetes, Gestational
/ drug therapy
Dose-Response Relationship, Drug
Female
Genetic Variation
Genotype
Glyburide
/ administration & dosage
Glycemic Control
/ methods
Humans
Hypoglycemia
/ epidemiology
Hypoglycemic Agents
/ administration & dosage
Polymorphism, Genetic
Pregnancy
Solute Carrier Organic Anion Transporter Family Member 1B3
/ genetics
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
27
05
2020
accepted:
25
11
2020
pubmed:
21
12
2020
medline:
28
7
2021
entrez:
20
12
2020
Statut:
ppublish
Résumé
Glyburide is mainly metabolized by the cytochrome P450 2C9 (CYP2C9) enzyme and enters the liver via the transporter OATP1B3. The variants OATP1B3*4 (699 G>A; rs7311358) and CYP2C9*2 and *3 are known to have a significant influence on the hepatic uptake and metabolism of glyburide, with lower clearance than in the wild type. In an ancillary study of the INDAO trial, we selected 117 pregnant women with gestational diabetes treated by glyburide and assessed the role of the combined CYP2C9 and OATP1B3 genetic polymorphisms in hypoglycemia and glycemic control. Three groups were constituted: (1) the wild-type genotype group (wild-type allele genotype for both CYP2C9*1 and OATP1B3*1 (699G)), (2) the intermediate group (carriers of CYP2C9*2 allele or OATP1B3*4 (699G>A) heterozygous), and (3) the variant group (carriers of CYP2C9*3 allele and/or OATP1B3*4 (699G>A) homozygous variant). We found that the risk of hypoglycemia was significantly higher in the variant genotype at the second week of treatment: 20.0% (4/20) vs. 8.1% (3/37) in the intermediate group and 4.1% (2/49) in the wild-type genotype group (P = 0.03). The last daily dose of glyburide during pregnancy was lower for patients in the variant genotype group: 4.7 mg (SD 3.5) vs. 8.7 mg (SD 5.7) in the wild-type group and 5.7 mg (SD 3.7) in the intermediate group (P < 0.01). In conclusion, the no-function variants CYP2C9*3 and OATP1B3*4 are associated with a higher risk of hypoglycemia and a lower dose of glyburide in women with gestational diabetes treated with glyburide, which is consistent with the pharmacokinetic roles of both CYP2C9 and OATP1B3.
Substances chimiques
Hypoglycemic Agents
0
SLCO1B3 protein, human
0
Solute Carrier Organic Anion Transporter Family Member 1B3
0
CYP2C9 protein, human
EC 1.14.13.-
Cytochrome P-450 CYP2C9
EC 1.14.13.-
Glyburide
SX6K58TVWC
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
141-148Informations de copyright
© 2020 The Authors. Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Références
Kirchheiner, J. & Brockmöller, J. Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin. Pharmacol. Ther. 77, 1-16 (2005).
Carbonell, N. et al. CYP2C9*3 loss-of-function allele is associated with acute upper gastrointestinal bleeding related to the use of NSAIDs other than aspirin. Clin. Pharmacol. Ther. 87, 693-698 (2010).
Teo, S.K. & Ee, C.H. Hypoglycaemia in the elderly. Singapore Med. J. 38, 432-434 (1997).
Asplund, K., Wiholm, B.E. & Lithner, F. Glibenclamide-associated hypoglycaemia: a report on 57 cases. Diabetologia 24, 412-417 (1983).
Holstein, A. et al. Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents. Br. J. Clin. Pharmacol. 60, 103-106 (2005).
Morin, S. et al. Pharmacogenetics of acenocoumarol pharmacodynamics. Clin. Pharmacol. Ther. 75, 403-414 (2004).
Theken, K.N. et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and nonsteroidal anti-inflammatory drugs. Clin. Pharmacol. Ther. 108, 191-200 (2020).
Yang, J.Q. et al. Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populations. Fundam. Clin. Pharmacol. 17, 373-376 (2003).
Niemi, M. et al. Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin. Pharmacol. Ther. 72, 326-332 (2002).
Kirchheiner, J. et al. Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin. Pharmacol. Ther. 71, 286-296 (2002).
Wang, R., Chen, K., Wen, S.Y., Li, J. & Wang, S.Q. Pharmacokinetics of glimepiride and cytochrome P450 2C9 genetic polymorphisms [2]. Clin. Pharmacol. Ther. 78, 90-92 (2005).
Yin, O.Q.P., Tomlinson, B. & Chow, M.S.S. CYP2C9, but not CYP2C19, polymorphisms affect the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects. Clin. Pharmacol. Ther. 78, 370-377 (2005).
Ragia, G., Petridis, I., Tavridou, A., Christakidis, D. & Manolopoulos, V.G. Presence of CYP2C9*3 allele increases risk for hypoglycemia in type 2 diabetic patients treated with sulfonylureas. Pharmacogenomics 10, 1781-1787 (2009).
Surendiran, A. et al. Influence of CYP2C9 gene polymorphisms on response to glibenclamide in type 2 diabetes mellitus patients. Eur. J. Clin. Pharmacol. 67, 797-801 (2011).
Klen, J., Dolžan, V. & Janež, A. CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea treatment in type 2 diabetes patients. Eur. J. Clin. Pharmacol. 70, 421-428 (2014).
Castelán-Martínez, O.D. et al. CYP2C9*3 gene variant contributes independently to glycaemic control in patients with type 2 diabetes treated with glibenclamide. J. Clin. Pharm. Ther. 43, 768-774 (2018).
Suzuki, K. et al. Effect of CYP2C9 genetic polymorphisms on the efficacy and pharmacokinetics of glimepiride in subjects with type 2 diabetes. Diabetes Res. Clin. Pract. 72, 148-154 (2006).
Zhou, K. et al. Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clin. Pharmacol. Ther. 87, 52-56 (2010).
Chen, Y. et al. Interaction of sulfonylureas with liver uptake transporters OATP1B1 and OATP1B3. Basic Clin. Pharmacol. Toxicol. 123, 147-154 (2018).
Yang, F. et al. OATP1B3 (699G>A) and CYP2C9*2, *3 significantly influenced the transport and metabolism of glibenclamide and glipizide. Sci. Rep. 8, 1-9 (2018).
Sénat, M.-V. et al. Effect of glyburide vs subcutaneous insulin on perinatal complications among women with gestational diabetes. JAMA 319, 1773 (2018).
Schwarz, U.I. et al. Identification of novel functional organic anion-transporting polypeptide 1B3 polymorphisms and assessment of substrate specificity. Pharmacogenet. Genomics 21, 103-114 (2011).
Yang, F. et al. CYP2C9 and OATP1B1 genetic polymorphisms affect the metabolism and transport of glimepiride and gliclazide. Sci. Rep. 8, 10994 (2018).
Royston, P. & Sauerbrei, W. A new approach to modelling interactions between treatment and continuous covariates in clinical trials by using fractional polynomials. Stat. Med. 23, 2509-2525 (2004).
Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285-291 (2016).
Becker, M.L. et al. Cytochrome P450 2C9 *2 and *3 polymorphisms and the dose and effect of sulfonylurea in type II diabetes mellitus. Clin. Pharmacol. Ther. 83, 288-292 (2008).
Zu Schwabedissen, H.E.M. et al. OATP1B3 is expressed in pancreatic b-islet cells and enhances the insulinotropic effect of the sulfonylurea derivative glibenclamide. Diabetes 63, 775-784 (2014).
Rothman, K.J. No adjustments are needed for multiple comparisons. Epidemiology 1, 43-46 (1990).