Effect of clarithromycin pre-treatment on the pharmacokinetics of metoclopramide after their simultaneous oral intake. (2nd August 2020)

• Record Type: Journal Article
• Authors: Kaukab, Iram; Shah, Syed Nisar Hussain; Kharaba, Zelal Jaber; Buabeid, Manal Ali; Alfoteih, Yaseen Abd; Murtaza, Ghulam
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 16:Number 8(2020)
• Page Start: 735
• Page End: 740
• Publication Date: 2020-08-02
• Subjects: Metoclopramide -- clarithromycin -- CYP3A4 inhibitors -- pharmacokinetics; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2020.1779699
• Languages: English
• ISSNs: 1742-5255

Abstract

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 Cmax, Tmax, and AUC0-∞ of metoclopramide were determined by analyzing the blood samples using a validated HPLC-UV method. Results: Clarithromycin increased the mean values of Cmax, AUC0-∞, and T1/2 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.