Part Two: Evaluation of N-methylbupropion as a Potential Bupropion Prodrug.

ABSTRACT: N-methylbupropion was selected as a potential prodrug from our in vitro screening of analogues of bupropion described in the preceding paper. This study describes in vivo pharmacokinetics of N-methylbupropion in the guinea-pig animal model, which is reported to best predict human metabolism of bupropion. The suitability of the guinea pig was established by studying N-demethylation of N-methylbupropion using S9 liver fractions. An LC-MS method was developed and validated to measure N-methylbupropion, bupropion and their metabolites in plasma and brain tissue. In separate studies, the prodrug was delivered by intraperitoneal injection (IP) to assess hepatic metabolism and then by oral gavage (PO) to assess the contribution from intestinal enzymes. Bupropion was administered in parallel. The

SUBMITTER: O'Byrne PM 

PROVIDER: S-EPMC4078515 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature