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Effect of adjuvant arthritis on the disposition of acebutolol enantiomers in rats.

PMID 1295378


Disease states such as arthritis may interact with the kinetics of beta-blockers. Acebutolol (AC) is a chiral beta-blocker which is available as a racemate. The beneficial properties of AC, however, is attributed mainly to the S-(+)-enantiomer. The disposition of AC enantiomers and their active, chiral metabolites, diacetolol (DC) were examined after oral administration to healthy and adjuvant-induced arthritic (AA) female Sprague-Dawley rats. Arthritis was induced by tail base injection of Mycobacterium butyricum. Swelling of hind and forepaws were apparent in 10-16 days in AA but not controls. Control and AA rats were sacrificed at 0.5, 1, 2, 4, 6 and 8 h after a 25 mg/kg oral AC dose and blood was collected (n = 6). Significant three to tenfold increases in the initial plasma concentrations (0.5-2 h) of AC were observed in AA. Enantiomers were equally affected, thus AC S:R ratio was not changed. Higher plasma concentrations of the metabolite were only significant at 2 h. The ratio of DC:AC, however, was unaffected by AA. The DC S:R ratio was significantly decreased at 0.5 and 1 h in AA. The limited protein binding of AC (10%) was neither stereoselective nor affected by AA. Reduced intrinsic clearance in AA may be responsible for these observations.

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Y0000359 Acebutolol impurity B, European Pharmacopoeia (EP) Reference Standard