Influence of Rifampicin Pre-treatment on the In vivo Pharmacokinetics of Metoclopramide in Pakistani Healthy Volunteers Following Concurrent Oral Administration
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Metoclopramide is metabolized by various cytochrome P450 (CYP) enzymes such as CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19. Rifampicin is a non-selective inducer of P-glycoprotein (P-gp) and CYP enzymes such as CYP3A4 and others.
OBJECTIVE: This study was aimed at the evaluation of rifampicin's enzyme induction effect on the pharmacokinetic parameters of orally administered metoclopramide.
METHOD: This randomized, single-blind, two-phase cross-over pharmacokinetic study separated by a 4-week washout period was conducted at a single center in Pakistan. It involved twelve Pakistani healthy male volunteers (nonsmokers) divided into two groups. In the reference phase, each volunteer received a single oral dose of 20 mg metoclopramide (Maxolon 10 mg, GlaxoSmithKline, Pakistan), while in the rifampicin-treated phase, each volunteer received 600 mg rifampicin once daily for 6 days through oral route. On day 6, metoclopramide (20 mg) was administered 2 hours after the last pretreatment dose of rifampicin. The serial blood samples were collected on predetermined time points (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 18 h) and analyzed using a validated HPLC method for the determination of pharmacokinetic parameters, i.e. Cmax, Tmax, and AUC0-∞ of metoclopramide. The whole study was monitored by an unblinded clinician for the purpose of volunteer's health safety.
RESULTS: All the volunteers participated in the study until the end. Twelve healthy Pakistani males having mean age 26.0 (range 20.6-34.1) years and body mass index 25.1 (range 16.2-31.5) kg/m2 were included in this study after taking written informed consent. Rifampicin significantly (P<0.05) decreased the mean Cmax, AUC0-∞ and T1/2 of metoclopramide by 35%, 68%, and 44%, respectively. The laboratory tests did not reveal any significant change in the biochemical, physical, hematological, or urinalytical values before and after metoclopramide treatment. None of the volunteers complained of any discomfort during the study.
CONCLUSION: Rifampicin noticeably decreased the concentration of plasma metoclopramide. These results give in vivo confirmation of the CYP3A4 involvement in the metoclopramide metabolism, in addition to CYP2D6. Therefore, metoclopramide pharmacokinetics may be clinically affected by rifampicin and other potent enzyme inducers.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Current drug metabolism - 21(2020), 4 vom: 17., Seite 301-306 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kaukab, Iram [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
CYP3A4 inducers |
|---|
| Anmerkungen: |
Date Completed 10.05.2021 Date Revised 10.05.2021 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.2174/1389200221666200514132654 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM309900808 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM309900808 | ||
| 003 | DE-627 | ||
| 005 | 20231225134924.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2174/1389200221666200514132654 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1032.xml |
| 035 | |a (DE-627)NLM309900808 | ||
| 035 | |a (NLM)32407272 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kaukab, Iram |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Influence of Rifampicin Pre-treatment on the In vivo Pharmacokinetics of Metoclopramide in Pakistani Healthy Volunteers Following Concurrent Oral Administration |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 10.05.2021 | ||
| 500 | |a Date Revised 10.05.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Metoclopramide is metabolized by various cytochrome P450 (CYP) enzymes such as CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19. Rifampicin is a non-selective inducer of P-glycoprotein (P-gp) and CYP enzymes such as CYP3A4 and others | ||
| 520 | |a OBJECTIVE: This study was aimed at the evaluation of rifampicin's enzyme induction effect on the pharmacokinetic parameters of orally administered metoclopramide | ||
| 520 | |a METHOD: This randomized, single-blind, two-phase cross-over pharmacokinetic study separated by a 4-week washout period was conducted at a single center in Pakistan. It involved twelve Pakistani healthy male volunteers (nonsmokers) divided into two groups. In the reference phase, each volunteer received a single oral dose of 20 mg metoclopramide (Maxolon 10 mg, GlaxoSmithKline, Pakistan), while in the rifampicin-treated phase, each volunteer received 600 mg rifampicin once daily for 6 days through oral route. On day 6, metoclopramide (20 mg) was administered 2 hours after the last pretreatment dose of rifampicin. The serial blood samples were collected on predetermined time points (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 18 h) and analyzed using a validated HPLC method for the determination of pharmacokinetic parameters, i.e. Cmax, Tmax, and AUC0-∞ of metoclopramide. The whole study was monitored by an unblinded clinician for the purpose of volunteer's health safety | ||
| 520 | |a RESULTS: All the volunteers participated in the study until the end. Twelve healthy Pakistani males having mean age 26.0 (range 20.6-34.1) years and body mass index 25.1 (range 16.2-31.5) kg/m2 were included in this study after taking written informed consent. Rifampicin significantly (P<0.05) decreased the mean Cmax, AUC0-∞ and T1/2 of metoclopramide by 35%, 68%, and 44%, respectively. The laboratory tests did not reveal any significant change in the biochemical, physical, hematological, or urinalytical values before and after metoclopramide treatment. None of the volunteers complained of any discomfort during the study | ||
| 520 | |a CONCLUSION: Rifampicin noticeably decreased the concentration of plasma metoclopramide. These results give in vivo confirmation of the CYP3A4 involvement in the metoclopramide metabolism, in addition to CYP2D6. Therefore, metoclopramide pharmacokinetics may be clinically affected by rifampicin and other potent enzyme inducers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CYP3A4 inducers | |
| 650 | 4 | |a Cytochrome 450 | |
| 650 | 4 | |a cross-over design | |
| 650 | 4 | |a metoclopramide | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a rifampicin. | |
| 650 | 7 | |a Cytochrome P-450 CYP3A Inducers |2 NLM | |
| 650 | 7 | |a Metoclopramide |2 NLM | |
| 650 | 7 | |a L4YEB44I46 |2 NLM | |
| 650 | 7 | |a Rifampin |2 NLM | |
| 650 | 7 | |a VJT6J7R4TR |2 NLM | |
| 700 | 1 | |a Shah, Syed Nisar Hussain |e verfasserin |4 aut | |
| 700 | 1 | |a Abrar, Muhammad Asad |e verfasserin |4 aut | |
| 700 | 1 | |a Anwer, Naveed |e verfasserin |4 aut | |
| 700 | 1 | |a Murtaza, Ghulam |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Current drug metabolism |d 2000 |g 21(2020), 4 vom: 17., Seite 301-306 |w (DE-627)NLM113669038 |x 1875-5453 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2020 |g number:4 |g day:17 |g pages:301-306 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2174/1389200221666200514132654 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2020 |e 4 |b 17 |h 301-306 | ||