Sultatos L G, Minor L D
Drug Metab Dispos. 1986 Mar-Apr;14(2):214-20.
Single-pass perfusion of mouse livers in situ with the phosphorothioate pesticide parathion resulted in formation of paraoxon, p-nitrophenol, p-nitrophenyl sulfate, and p-nitrophenyl-beta-D-glucuronide. At a perfusate bovine serum albumin (BSA) concentration of 4% (fraction of unbound parathion = 0.04), and a flow rate of 3.2 ml/min/liver, the half-life associated with the approach to steady state of parathion was 6.2 min (SD = 0.4), whereas at steady state the extraction ratio of parathion was 0.19 (SD = 0.03). Alterations in perfusate flow rates had no discernable effects on metabolism of parathion. However, lowering the BSA perfusate concentration to 1.0% (fraction of unbound parathion = 0.12) significantly prolonged the half-life for the approach to steady state while increasing the steady state extraction ratio to 0.49 (SD = 0.08). At perfusate BSA concentrations below 1%, steady state conditions with respect to parathion could not be achieved during the 50-min perfusions. These results suggest that binding of parathion to BSA hinders its biotransformation by mouse livers perfused in situ, probably by limiting the availability of free pesticide to metabolic sites. Consequently, its elimination by the liver is insensitive to changes in hepatic blood flow. However, exclusion of BSA from the perfusate resulted in partitioning of all parathion in perfusate into the liver, leading to high concentrations of parathion within liver and preventing biotransformation of this pesticide.
用硫代磷酸酯农药对硫磷对小鼠肝脏进行单次原位灌注，会导致对氧磷、对硝基苯酚、对硝基苯硫酸酯和对硝基苯基-β-D-葡萄糖醛酸苷的形成。在灌注液中牛血清白蛋白（BSA）浓度为4%（未结合对硫磷的比例 = 0.04）且流速为3.2毫升/分钟/肝脏的情况下，对硫磷达到稳态的半衰期为6.2分钟（标准差 = 0.4），而在稳态时对硫磷的提取率为0.19（标准差 = 0.03）。灌注液流速的改变对对硫磷的代谢没有明显影响。然而，将BSA灌注液浓度降至1.0%（未结合对硫磷的比例 = 0.12）会显著延长达到稳态的半衰期，同时将稳态提取率提高到0.49（标准差 = 0.08）。在灌注液BSA浓度低于1%时，在50分钟的灌注过程中无法达到对硫磷的稳态条件。这些结果表明，对硫磷与BSA的结合会阻碍其在原位灌注的小鼠肝脏中的生物转化，可能是通过限制游离农药到达代谢位点的可用性。因此，肝脏对其清除对肝血流量变化不敏感。然而，从灌注液中排除BSA会导致灌注液中所有对硫磷都进入肝脏，导致肝脏内对硫磷浓度过高，并阻止这种农药的生物转化。
