Effect of clarithromycin pre-treatment on the pharmacokinetics of metoclopramide after their simultaneous oral intake
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
Expert opinion on drug metabolism & toxicology - 16(2020), 8 vom: 11. Aug., Seite 735-740 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kaukab, Iram [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.03.2021 Date Revised 12.03.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/17425255.2020.1779699 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311041264 |
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| 245 | 1 | 0 | |a Effect of clarithromycin pre-treatment on the pharmacokinetics of metoclopramide after their simultaneous oral intake |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a RESULTS: Clarithromycin increased the mean values of Cmax, AUC0-∞, and T1/2 of metoclopramide by 46%, 78.6%, and 9.8%, respectively | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a CYP3A4 inhibitors | |
| 650 | 4 | |a Metoclopramide | |
| 650 | 4 | |a clarithromycin | |
| 650 | 4 | |a pharmacokinetics | |
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| 650 | 7 | |a Antiemetics |2 NLM | |
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| 700 | 1 | |a Kharaba, Zelal Jaber |e verfasserin |4 aut | |
| 700 | 1 | |a Buabeid, Manal Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Alfoteih, Yaseen Abd |e verfasserin |4 aut | |
| 700 | 1 | |a Murtaza, Ghulam |e verfasserin |4 aut | |
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