Effect of misoprostol on the pharmacokinetics of sustained release diclofenac in Myanmar healthy male volunteers

Authors

  • Htet Htet Aung Department of Pharmacology, University of Medicine (2), Yangon
  • Aye Soe Department of Pharmacology, University of Medicine (2), Yangon
  • Nu Nu Aye Department of Pharmacology, University of Medicine (2), Yangon

Keywords:

Diclofenac SR, misoprostol, pharmacokinetics

Abstract

Background: Sustained release diclofenac (diclofenac SR) is the commonly used non-steroidal anti-inflammatory drug for chronic inflammatory conditions such as rheumatoid arthritis.Misoprostol, prostaglandin analogue, is the agent that enhances gastrointestinal mucosal defense. Concomitant administration of misoprostol with diclofenac SR can prevent the gastrointestinal side effects of diclofenac SR.
Objective: The purpose of the study was to explore the effect of misoprostol on the pharmacokinetics of diclofenac SR in healthy volunteers.
Methods: Crossover study was evaluated in 14 male volunteers. Single oral dose of 100 mg diclofenac SR was concomitantly administered with 200 µg misoprostol with one-week wash out period. Plasma concentrations at 0, 0.5, 1, 1.5, 2, 3, 6 and 10 hrs were determined by high performance liquid chromatography (HPLC). Pharmacokinetic parameters such as area under concentration-time curve     (AUC0-∞), peak plasma concentration (Cmax), time to achieve peak plasma concentration (Tmax), absorption half-life (T½(ab)), elimination half-life (T1/2(el)), absorption rate constant (Kab), and elimination rate constant (Kel) were determined.
Results: With misoprostol, the mean AUC0-∞ of diclofenac SR was significantly reduced from 12.11±5.25µg/mL×hr to 4.17±2.72µg/mL×hr (p<0.001). The mean Cmax was also significantly decreased from 1.43±0.46 µg/mL to 0.98±0.48 µg/mL (p<0.05). The mean Tmax was decreased from 1.61±0.53hr to 1.46±0.41hr (p>0.05). The mean T½(ab) was decreased from 0.56±0.23hr to 0.54±0.19hr (p>0.05). The mean Kab were almost the same 1.43±0.54hr-1 and 1.43±0.48hr-1. The mean T1/2(el) was decreased from 3.68±1.64hr to 3.03±1.08hr (p>0.05). The mean Kel was increased from 0.21±0.09hr-1 to 0.25±0.09hr-1 (p>0.05).
Conclusion: There was a significant reduction in the extent of absorption of diclofenac SR when concomitantly administered with misoprostol. Therefore, the dose of diclofenac SR may need to be increased to avoid therapeutic failure of diclofenac SR or concurrent use with misoprostol may need to be changed to other gastroprotective agents.

 

Downloads

Published

24-03-2017

How to Cite

Aung, H. H., Soe, A., & Aye, N. N. (2017). Effect of misoprostol on the pharmacokinetics of sustained release diclofenac in Myanmar healthy male volunteers. Siriraj Medical Journal, 69(2), 75–79. Retrieved from https://he02.tci-thaijo.org/index.php/sirirajmedj/article/view/80895

Issue

Vol. 69 No. 2 (2017): March-April

Section

Original Article

License

Authors who publish with this journal agree to the following conditions:

Copyright Transfer

In submitting a manuscript, the authors acknowledge that the work will become the copyrighted property of Siriraj Medical Journal upon publication.

License

 Articles are licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). This license allows for the sharing of the work for non-commercial purposes with proper attribution to the authors and the journal. However, it does not permit modifications or the creation of derivative works.

Sharing and Access

Authors are encouraged to share their article on their personal or institutional websites and through other non-commercial platforms. Doing so can increase readership and citations.