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Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype.
Dujic, Tanja; Cvijic, Sandra; Elezovic, Amar; Bego, Tamer; Imamovic Kadric, Selma; Malenica, Maja; Elezovic, Alisa; Pearson, Ewan R; Kulo, Aida.
Affiliation
  • Dujic T; Department of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina.
  • Cvijic S; Department of Pharmaceutical Technology and Cosmetology, University of Belgrade-Faculty of Pharmacy, 11221 Belgrade, Serbia.
  • Elezovic A; Control Laboratory, Agency for Medicines and Medical Devices of Bosnia and Herzegovina, 71000 Sarajevo, Bosnia and Herzegovina.
  • Bego T; Department of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina.
  • Imamovic Kadric S; Department of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina.
  • Malenica M; Department of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina.
  • Elezovic A; Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina.
  • Pearson ER; Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, UK.
  • Kulo A; Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, 71000 Sarajevo, Bosnia and Herzegovina.
J Pers Med ; 11(5)2021 May 03.
Article in En | MEDLINE | ID: mdl-34063566
The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4-1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6- and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: J Pers Med Year: 2021 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: J Pers Med Year: 2021 Document type: Article