Effect of clarithromycin pre-treatment on the pharmacokinetics of metoclopramide after their simultaneous oral intake

ABSTRACT

Objective

The objective of this study was to assess the influence of enzyme suppression on the values of various pharmacokinetic factors of orally administered metoclopramide.

Method

This study was conducted in two phases and a 4-week duration was adopted for drug washout. This randomized study involved 12 healthy human volunteers who received a single oral dose of metoclopramide 20 mg. After the washout period, volunteers received clarithromycin 500 mg two times per day for consecutive 5 days. On test day (fifth day), a single oral dose of metoclopramide 20 mg was also given to the volunteers, and collection of blood samples was conducted at pre-decided time points. Various pharmacokinetic parameters such as C_max, T_max, and AUC_0-∞ of metoclopramide were determined by analyzing the blood samples using a validated HPLC-UV method.

Results

Clarithromycin increased the mean values of C_max, AUC_0-∞, and T_1/2 of metoclopramide by 46%, 78.6%, and 9.8%, respectively.

Conclusion

Clarithromycin noticeably increased the concentration of plasma metoclopramide. This study’s results provide in vivo confirmation of the CYP3A4 involvement in metoclopramide metabolism, in addition to CYP2D6. Therefore, metoclopramide pharmacokinetics may be clinically affected by clarithromycin and other potent enzyme inhibitors.

KEYWORDS:

• Metoclopramide
• clarithromycin
• CYP3A4 inhibitors
• pharmacokinetics

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

I Kaukab, SNH Shah, ZJ Kharaba, MA Buabeid, and G Murtaza design this study. I Kaukab and G Murtaza performed the experiments. SNH Shah supervised this work. YA Alfoteih improved the English language quality.

Additional information

Funding

This paper was not funded.