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Pharmacokinetis of alpha- and beta-isomers of racemic endosulfan following intravenous administration in rabbits.
The pharmacokinetics of the alpha- and beta-isomers of endosulfan in rabbits was investigated following intravenous injection. Endosulfan (2 mg/kg) was given as a mixture of the two isomers in the ratio 70:30. The plasma concentration-time data for alpha-endosulfan was best fitted to the three-compartment model with a terminal slope half-life of 235 +/- 168 (SD; N = 6) hr. The data for beta-endosulfan was adequately described by the two-compartment model, the corresponding half-life was 5.97 +/- 2.41 hr. The total distribution volumes during the terminal slopes were, however, similar for alpha- and beta-endosulfan (675 +/- 246 and 565 +/- 126 ml/kg, respectively). Consequently, the plasma clearance was considerably lower for alpha-endosulfan (2.70 +/- 1.3 ml/hr/kg) than for beta-endosulfan (70.1 +/- 18.6 ml/hr/kg). The alpha-isomer had a higher fraction unchanged in the urine (37% of dose) than did the beta-isomer (11%) and a slightly higher fraction unchanged in feces (2.7% and 0.4%, respectively) at 5 days. Thus, the two isomers of endosulfan showed pronounced differences in their pharmacokinetic profile. These dissimilarities may partly explain reported differences in toxicity between the alpha- and beta-isomer.
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