TY  - JOUR
AU  - Dujić, Tanja
AU  - Cvijić, Sandra
AU  - Elezović, Amar
AU  - Bego, Tamer
AU  - Imamović Kadrić, Selma
AU  - Malenica, Maja
AU  - Elezović, Alisa
AU  - Pearson, Ewan R.
AU  - Kulo, Aida
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4087
AB  - 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.
PB  - MDPI
T2  - Journal of Personalized Medicine
T1  - Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype
VL  - 11
IS  - 5
DO  - 10.3390/jpm11050367
ER  - 

@article{
author = "Dujić, Tanja and Cvijić, Sandra and Elezović, Amar and Bego, Tamer and Imamović Kadrić, Selma and Malenica, Maja and Elezović, Alisa and Pearson, Ewan R. and Kulo, Aida",
year = "2021",
abstract = "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.",
publisher = "MDPI",
journal = "Journal of Personalized Medicine",
title = "Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype",
volume = "11",
number = "5",
doi = "10.3390/jpm11050367"
}

Dujić, T., Cvijić, S., Elezović, A., Bego, T., Imamović Kadrić, S., Malenica, M., Elezović, A., Pearson, E. R.,& Kulo, A.. (2021). Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype. in Journal of Personalized Medicine
MDPI., 11(5).
https://doi.org/10.3390/jpm11050367

Dujić T, Cvijić S, Elezović A, Bego T, Imamović Kadrić S, Malenica M, Elezović A, Pearson ER, Kulo A. Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype. in Journal of Personalized Medicine. 2021;11(5).
doi:10.3390/jpm11050367 .

Dujić, Tanja, Cvijić, Sandra, Elezović, Amar, Bego, Tamer, Imamović Kadrić, Selma, Malenica, Maja, Elezović, Alisa, Pearson, Ewan R., Kulo, Aida, "Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype" in Journal of Personalized Medicine, 11, no. 5 (2021),
https://doi.org/10.3390/jpm11050367 . .