Mosha R D, Gyrd-Hansen N, Nielsen P
Department of Pharmacology and Toxicology, Royal Veterinary and Agricultural University, Bülowsvej 13, Frederiksberg, Denmark.
Pharmacol Toxicol. 1990 Sep;67(3):246-51. doi: 10.1111/j.1600-0773.1990.tb00822.x.
Toxicokinetic parameters and cumulative excretion were studied in goats after intravenous, oral and dermal administration of unlabelled and 14C-ethion. Plasma concentration-time data was subjected to non-compartmental analysis. IV injection studies showed an effective half-life (t1/2) of 2 hr, a total body clearance (ClT) of 3.21.kg-1.hr-1 and a volume of distribution (Vd(ss) of 9.4 1.kg-1. Plasma levels of 14C-ethion (ethion + metabolites) were much higher and more persistent than those of unchanged ethion. Cumulative excretion of 14C-ethion was 78% of the dose with 66% in urine, 8% in faeces and 4% in milk. Oral administration resulted in low plasma levels of unchanged ethion, an absorption half-life (t1/2 abs) of 10 hr and a bioavailability of less than 5%. Cumulative excretion was 80% of the dose with 64% in urine, 14% in faeces and 1.7% in milk. Dermal application showed a t1/2 abs of 85 hr and a bioavailability of 20%. Only 0.05% of the dose was excreted unchanged in milk. It is concluded that (1) orally administered ethion is extensively metabolized in the GIT, (2) dermal application results in prolonged and limited absorption and (3) absorbed ethion is rapidly eliminated through metabolism.
在山羊静脉注射、口服和经皮给予未标记的乙硫磷及14C - 乙硫磷后，研究了其毒代动力学参数和累积排泄情况。血浆浓度 - 时间数据进行了非房室分析。静脉注射研究显示，有效半衰期（t1/2）为2小时，全身清除率（ClT）为3.21.kg-1.hr-1，分布容积（Vd(ss)）为9.4 1.kg-1。14C - 乙硫磷（乙硫磷 + 代谢物）的血浆水平比未变化的乙硫磷高得多且更持久。14C - 乙硫磷的累积排泄量为剂量的78%，其中66%经尿液排泄，8%经粪便排泄，4%经乳汁排泄。口服给药导致未变化的乙硫磷血浆水平较低，吸收半衰期（t1/2 abs）为10小时，生物利用度小于5%。累积排泄量为剂量的80%，其中64%经尿液排泄，14%经粪便排泄，1.7%经乳汁排泄。经皮给药显示吸收半衰期（t1/2 abs）为85小时，生物利用度为20%。仅0.05%的剂量以未变化形式经乳汁排泄。结论为：（1）口服乙硫磷在胃肠道中广泛代谢；（2）经皮给药导致吸收延长且有限；（3）吸收的乙硫磷通过代谢迅速消除。
