Title: Comparative pharmacokinetics of quinidine and Its O-desmethyl metabolite in rabbits
Abstract: <h2>Abstract</h2> The pharmacokinetics of quinidine and the <i>O</i>-desmethyl metabolite 6′-hydroxycinchonine were studied in rabbits. After intravenous bolus injections of equimolar doses, the blood concentration–time curves of each agent declined biexponentially, which was characteristic of a two-compartment open model. A significant difference between quinidine and 6′-hydroxycinchonine was observed for the following parameters: ±, and the intercompartmental distribution ratio, <i>k</i><sub>12</sub>/<i>k</i><sub>21</sub>. The results showed that the distribution of the metabolite was slower than quinidine and suggested that it <i>also</i> was less extensive. The <i>Vd</i><sub>β</sub> value for 6′-hydroxycinchonine was approximately one-half of the value observed for quinidine, and its <i>k</i><sub>12</sub>/<i>k</i><sub>21</sub> ratio was about one-fourth of the quinidine value. The terminal half-lives for quinidine and the metabolite were 132.4 ± 27.1 and 65.4 ± 34.4 min, respectively. Total body clearance was similar for both compounds. The findings of this study could be explained by the greater polarity or greater water solubility of 6′-hydroxycinchonine. The limited data in humans coupled with the results of this investigation suggest that, although it is intrinsically active, the <i>O</i>-demethylated metabolite probably contributes little to the anti-arrhythmic effects seen after quinidine administration in humans.
Publication Year: 1980
Publication Date: 1980-12-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 9
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