Metabolism of bromhexine in pig hepatocyte cultures

Authors: L. A. Meijer¹; J. C. M. Verstegen¹; S. Bull²; J. Fink-Gremmels²

Source: Journal of Veterinary Pharmacology & Therapeutics, Volume 27, Number 4, August 2004 , pp. 219-225(7)

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Abstract:

Meijer, L. A., Verstegen, J. C. M., Bull, S., Fink-Gremmels, J. Metabolism of bromhexine in pig hepatocyte cultures. J. vet. Pharmacol. Therap.27, 219–225.

The metabolism of bromhexine [N-cyclohexyl-N-methyl-2-(2-amino-3,5-di-bromo-benzyl)-amine] was studied using pig hepatocyte cultures and LC/MS/MS techniques. Phase I ‘single-step’ reactions, i.e. hydroxylation and demethylation occurred the fastest whereas the formation of hydroxylated/demethylated and aminal hydroxylated metabolites, which can be considered as multiple-step reactions, occurred more slowly. Phase II conjugates were detected for all hydroxylated metabolites. The glucuronides of the hydroxylated/demethylated components tended to accumulate. In addition to metabolites known to be formed in vivo, three unknown components related to bromhexine were detected. Two of these metabolites accumulated during incubation. Based on the fragmentation patterns, a possible molecular structure is proposed for these components.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2885.2004.00584.x

Affiliations: 1: Dopharma Research, Raamsdonksveer; 2: Department of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands

Publication date: 2004-08-01