Effect of chloroquine pre-treatment on the metoclopramide’s pharmacokinetics after their co-administration

ABSTRACT

Background

This study evaluated the pharmacokinetic interactions of orally administered chloroquine and metoclopramide.

Methods

The study employed a randomized and two-phase cross-over design with four weeks washout plan. Twelve healthy male volunteers were shortlisted according to the set criteria and were administered with metoclopramide 10 mg PO, and chloroquine (a total of 1500 mg) at different intervals which were (500 mg at 0, 6, and 24 h). The concentration of chloroquine and metoclopramide in the blood samples was estimated using a validated HPLC-UV technique to affirm the maximum concentration (C_max), time to reach C_max (T_max), and area under the curve (AUC).

Results

C_max, T_1/2, and AUC of metoclopramide were increased up to 20, 10, and 47.8% respectively by the concomitantly administering Chloroquine. Chloroquine-treated phase showed increased values of Cmax (ng/ml), AUC (ng.h/ml), and T_½ (h), i.e. 41.35 ± 1.61, 504.12 ± 66.25 and 5.72 ± 2.63, as compared to that Reference phase i.e. 34.52 ± 4.92, 341.14 ± 112.8, and 5.19 ± 1.14, respectively.

Conclusions

Chloroquine was found to attenuate CYP2D6 activity in healthy Pakistani male volunteers. Hence, patients that are prescribed with metoclopramide or other CYP2D6-substrate drugs require a dose adjustment when administered with chloroquine.

KEYWORDS:

• Metoclopramide
• chloroquine
• CYP2D6 inhibitors
• pharmacokinetics

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Declaration of interests

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 contribution statement

Badriyah Shadid Alotaibi, Iram Kaukab, Syed Nisar Hussain Shah, Abdul Rafay Naeem, Haya Yasin, Muhammad Ihtisham Umar, and Ghulam Murtaza design this study. Iram Kaukab, Syed Nisar Hussain Shah, Abdul Rafay Naeem, Ghulam Murtaza performed the experiments. Syed Nisar Hussain Shah supervised this work. Badriyah Shadid Alotaibi, Abdul Rafay Naeem, Haya Yasin, Muhammad Ihtisham Umar, Ghulam Murtaza improved the English language quality.

Ethics Statement

Formal permission (Approval No. 2720/PEC/2016) for experimental studies was obtained from the Departmental Ethical Committee for Research, Bahaudin Zakariya University (BZU) Multan, Pakistan.

Between 24 and 34 years and the body mass index (BMI) between 16 and 31 kg/m2 were registered in the study after acquiring their written consent.

Additional information

Funding

We acknowledge Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R73), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia for supporting this study. We extend our appreciation to the Deanship of Graduate Studies at Ajman University, Ajman, United Arab Emirates, for their support to this work.