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Benorylate hydrolysis by human plasma and human liver
F M Williams1, U Moore, R A Seymour
1Wolfson Unit of Clinical Pharmacology, Department of Operative Dentistry, Medical School, University of Newcastle upon Tyne.
British Journal of Clinical Pharmacology
|December 1, 1989
Summary
Benorylate hydrolysis in the body primarily yields salicylate and paracetamol. These active metabolites, produced mainly in the liver cytosol, are responsible for benorylate's therapeutic effects.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Biochemistry
Background:
- Benorylate is a combination drug used for its anti-inflammatory and analgesic properties.
- Understanding its metabolic pathways is crucial for assessing its efficacy and safety.
Purpose of the Study:
- To investigate the in vitro hydrolysis of benorylate by human plasma, liver microsomes, and cytosol.
- To identify the primary metabolites of benorylate.
- To correlate in vivo findings with in vitro metabolic data.
Main Methods:
- In vitro incubation of benorylate with human plasma, liver microsomes, and cytosol.
- Analysis of hydrolysis products using biochemical assays.
- Detection of metabolites in plasma samples from volunteers after oral benorylate administration.
Main Results:
- Benorylate hydrolysis proceeds via initial deacetylation to phenetsal, followed by hydrolysis to paracetamol and salicylate.
- Liver cytosol demonstrated higher hydrolytic activity compared to microsomes and plasma.
- In vivo studies confirmed the presence of only salicylate and paracetamol in volunteer plasma after benorylate administration.
Conclusions:
- The primary route of benorylate metabolism involves sequential hydrolysis yielding paracetamol and salicylate.
- Human liver cytosol is the main site for benorylate hydrolysis.
- The therapeutic effects of benorylate are attributed to its active metabolites, salicylate and paracetamol.