Gupta P K, Ehrnebo M
Drug Metab Dispos. 1979 Jan-Feb;7(1):7-10.
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.
静脉注射后，研究了硫丹α-异构体和β-异构体在兔体内的药代动力学。硫丹（2mg/kg）以两种异构体70:30的比例混合给药。α-硫丹的血浆浓度-时间数据最适合三室模型，终末斜率半衰期为235±168（标准差；N=6）小时。β-硫丹的数据可用二室模型充分描述，相应半衰期为5.97±2.41小时。然而，α-硫丹和β-硫丹在终末斜率期间的总分布容积相似（分别为675±246和565±126ml/kg）。因此，α-硫丹的血浆清除率（2.70±1.3ml/小时/千克）比β-硫丹（70.1±18.6ml/小时/千克）低得多。在第5天时，α-异构体在尿液中未变化的部分（占剂量的37%）高于β-异构体（11%），在粪便中未变化的部分略高（分别为2.7%和0.4%）。因此，硫丹的两种异构体在药代动力学特征上表现出明显差异。这些差异可能部分解释了α-异构体和β-异构体之间报道的毒性差异。
