Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype
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 app...
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MDPI AG
2021-05-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/11/5/367 |
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| author | Tanja Dujic Sandra Cvijic Amar Elezovic Tamer Bego Selma Imamovic Kadric Maja Malenica Alisa Elezovic Ewan R. Pearson Aida Kulo |
| author_facet | Tanja Dujic Sandra Cvijic Amar Elezovic Tamer Bego Selma Imamovic Kadric Maja Malenica Alisa Elezovic Ewan R. Pearson Aida Kulo |
| author_sort | Tanja Dujic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:44:10Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T11:44:10Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-43967b59cc724390a6810ee03ac106b22023-11-21T18:14:32ZengMDPI AGJournal of Personalized Medicine2075-44262021-05-0111536710.3390/jpm11050367Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 PhenotypeTanja Dujic0Sandra Cvijic1Amar Elezovic2Tamer Bego3Selma Imamovic Kadric4Maja Malenica5Alisa Elezovic6Ewan R. Pearson7Aida Kulo8Department of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Pharmaceutical Technology and Cosmetology, University of Belgrade-Faculty of Pharmacy, 11221 Belgrade, SerbiaControl Laboratory, Agency for Medicines and Medical Devices of Bosnia and Herzegovina, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Biochemistry & Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and HerzegovinaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, 71000 Sarajevo, Bosnia and HerzegovinaDivision of Population Health & Genomics, School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, UKDepartment of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, 71000 Sarajevo, Bosnia and HerzegovinaThe 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.https://www.mdpi.com/2075-4426/11/5/367omeprazolegliclazideCYP2C19physiologically based pharmacokinetic modelingdrug–drug interactiondrug–drug–gene interaction |
| spellingShingle | Tanja Dujic Sandra Cvijic Amar Elezovic Tamer Bego Selma Imamovic Kadric Maja Malenica Alisa Elezovic Ewan R. Pearson Aida Kulo Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype Journal of Personalized Medicine omeprazole gliclazide CYP2C19 physiologically based pharmacokinetic modeling drug–drug interaction drug–drug–gene interaction |
| title | Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype |
| title_full | Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype |
| title_fullStr | Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype |
| title_full_unstemmed | Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype |
| title_short | Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype |
| title_sort | interaction between omeprazole and gliclazide in relation to cyp2c19 phenotype |
| topic | omeprazole gliclazide CYP2C19 physiologically based pharmacokinetic modeling drug–drug interaction drug–drug–gene interaction |
| url | https://www.mdpi.com/2075-4426/11/5/367 |
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