Effect of clopidogrel on the hydroxylation and sulfoxidation of omeprazole: A single dose study in healthy human volunteers

Authors

  • Lateef Ahmad Department of Pharmacy, University of Swabi, Khyber Pakhtunkhwa, Pakistan
  • Zafar Iqbal Department of Pharmacy, University of Peshawar, Peshawar, Khyber-Pakhtunkhwa, Pakistan
  • Shabnam Nazir Department of Pharmacy, Kohat University of Science and Technology, Khyber Pakhtunkhwa, Pakistan
  • Abad Khan Department of Pharmacy, University of Swabi, Khyber Pakhtunkhwa, Pakistan
  • Yasar Shah Department of Pharmacy, Abdul Wali Khan University, Khyber Pakhtunkhwa, Pakistan
  • Muhammad Imran Khan Department of Pharmacy, Women Institute of Learning, Abbottabad
  • Ismail Khan Department of Pharmacy, University of Peshawar, Peshawar, Khyber-Pakhtunkhwa, Pakistan
  • Amjad Khan Department of Pharmacy, Abasyn University, Khyber Pakhtunkhwa, Pakistan

DOI:

https://doi.org/10.17179/excli2016-658

Keywords:

clopidogrel, omeprazole, drug interactions, pharmacokinetics, poor metabolizers, extensive metabolizers

Abstract

Based upon the known potential interaction between omeprazole (OMP) and clopidogrel (CLOP), the current study was designed to evaluate the effect of CLOP on disposition of OMP and its two major metabolites, 5-hydroxyomeprazole (5-OH-OMP) and omeprazole sulfone (OMP-S) in healthy clinical subjects. A randomized, open label, 2-period, crossover study was designed. Twelve volunteers were selected, of whom eight were extensive metabolizers (EM) of CYP2C19 and 4 were poor metabolizers (PM). They received single dose of OMP either alone or in combination with CLOP (single dose) and samples were collected periodically to calculate various pharmacokinetic parameters. Changes in most of the pharmacokinetic parameters of OMP, 5-OH-OMP and OMP-S were insignificant (P ˃ 0.05) both in EM and PM except for the maximum concentration (Cmax) of 5-OH-OMP and OMP-S in EM. The OMP Cmax and AUC0-∞ was increased both in EM and PM after concomitant administration of OMP with CLOP. The 5-OH-OMP Cmax was decreased in both EM and PM, demonstrating that CLOP inhibits hydroxylation of OMP. The OMP-S Cmax and AUC0-∞ were increased both in EM and PM showing that CLOP may induce sulfoxidation of OMP. It was concluded that CLOP may inhibit hydroxylation of OMP to a greater extent in EM than in PM, leading to higher OMP Cmax and AUC0-∞. Furthermore, the sulfoxidation of OMP may also be induced by CLOP. So, it is suggested that both these drugs should be carefully prescribed together to avoid any harm to the patients. (Application number13/EC/Pharm. Ref number 12/Pharm).

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Published

2017-03-22

How to Cite

Ahmad, L., Iqbal, Z., Nazir, S., Khan, A., Shah, Y., Khan, M. I., … Khan, A. (2017). Effect of clopidogrel on the hydroxylation and sulfoxidation of omeprazole: A single dose study in healthy human volunteers. EXCLI Journal, 16, 321–327. https://doi.org/10.17179/excli2016-658

Issue

Vol. 16 (2017)

Section

Original articles

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