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The Stereoselective Disposition of Disopyramide in the Dog

Giacomini Kathleen M.; Giacomini, John C.; Swezey, Sarah E.; Harrison, Donald C.; Nelson, Wendel L.; Burke, Terrence R. Jr.; Blaschke, Terrence F.
Journal of Cardiovascular Pharmacology: November-December 1980
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The disposition of d-, l-, and d,l-disopyramide was studied in 5 conscious dogs after intravenous administration (15 mg/kg) of each compound using a balanced crossover design. The clearance of d-disopyramide (15.4 ± 5.10 ml/min/kg) was significantly greater than that of the l-isomer (9.45 ± 2.52 ml/min/kg) (p < 0.001). The clearance of the d,l,-mixture was intermediate between that obtained for the d-and l-isomers. The steady-state volume of distribution of the three compounds was similar (approximately 1.4 liters/kg). The elimination half-life reflected differences in clearance, being 76.4 ± 7.30 min for d-disopyramide, 112 ± 23.4 min for l-disopyramide, and 97.2 ± 15.1 min for d,l-disopyramide. The effect of general anesthesia with urethane and chloralose on the disposition of the compounds was also examined. General anesthesia decreased the clearance and increased the half-life of all three compounds. No consistent differences in the volume of distribution were observed with anesthesia as compared to control. Thus, there is stereoselective elimination of the optical isomers of disopyramide in the dog, and general anesthesia decreases the clearance of d-, l-, and d,l-disopyramide.

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