Facile hydrolysis of mebeverine in vitro and in vivo: Negligible circulating concentrations of the drug after oral administration

Dickinson R.G., Baker P.V., Franklin M.E. and Hooper W.D. (1991) Facile hydrolysis of mebeverine in vitro and in vivo: Negligible circulating concentrations of the drug after oral administration. Journal of Pharmaceutical Sciences, 80 10: 952-957. doi:10.1002/jps.2600801010


Author Dickinson R.G.
Baker P.V.
Franklin M.E.
Hooper W.D.
Title Facile hydrolysis of mebeverine in vitro and in vivo: Negligible circulating concentrations of the drug after oral administration
Journal name Journal of Pharmaceutical Sciences   Check publisher's open access policy
ISSN 0022-3549
Publication date 1991-01-01
Sub-type Article (original research)
DOI 10.1002/jps.2600801010
Open Access Status Not yet assessed
Volume 80
Issue 10
Start page 952
End page 957
Total pages 6
Language eng
Subject 1313 Molecular Medicine
1600 Chemistry
1605 Policy and Administration
3002 Drug Discovery
3003 Pharmaceutical Science
3004 Pharmacology
Abstract The HPLC methods for the determination of plasma concentrations of the antispasmodic agent mebeverine (0.01–10 μ/mL) and its hydrolysis product veratric acid (0.1–50 μg/mL) are presented. Mebeverine was demonstrated to hydrolyze readily in fresh unbuffered human and rat plasma samples ex vivo. Hydrolysis in human plasma was completely inhibited in the presence of the esterase inhibitor physostigmine sulfate, at a concentration of 130 μg/mL. However, the inhibitor was only partially effective in blocking mebeverine hydrolysis in rat plasma. After oral administration of mebeverine · HCI (270 mg) to fasted human volunteers, measurable concentrations of the drug were not found in plasma. By contrast, the metabolite veratric acid achieved considerable concentrations (mean peak plasma concentration of 13.5 μg/mL at 40–80 min). After iv administration of mebeverine · HCI (2 mg) to rats, the drug was rapidly eliminated from plasma (mean half‐life of 29 min) with simultaneous appearance of veratric acid (mean peak plasma concentration of 1.80 μg/mL at 15–30 min). However, after oral administration of the same dose, only traces of mebeverine were found in plasma, with the exception of one rat. Veratric acid again achieved considerable concentrations (mean peak plasma concentration of 0.90 μg/mL at 15 min‐4 h). The results show that mebeverine undergoes rapid and extensive first‐pass metabolism involving hydrolysis of the ester function, and that negligible circulating concentrations of the parent drug are found in humans. Copyright
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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Created: Tue, 26 Jul 2016, 14:42:23 EST by System User