2,6-二氯硫代苯甲酰胺（前缀）与2,6-二氯苯腈在犬类和大鼠体内的代谢比较

The comparative metabolism of 2,6-dichlorothiobenzamide (Prefix) and 2,6-dichlorobenzonitrile in the dog and rat.

作者信息

Griffiths M H, Moss J A, Rose J A, Hathway D E

出版信息

Biochem J. 1966 Mar;98(3):770-81. doi: 10.1042/bj0980770.

DOI:10.1042/bj0980770

PMID:5911525

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1264918/

Abstract

A single oral dose of either [(14)C]Prefix or 2,6-dichlorobenzo[(14)C]nitrile to rats is almost entirely eliminated in 4 days: 84.8-100.5% of (14)C from [(14)C]Prefix is excreted, 67.3-79.7% in the urine, and 85.8-97.2% of (14)C from 2,6-dichlorobenzo-[(14)C]nitrile is excreted, 72.3-80.7% in the urine. Only 0.37+/-0.03% of the dose of [(14)C]Prefix and 0.25+/-0.03% of the dose of 2,6-dichlorobenzo[(14)C]nitrile are present in the carcass plus viscera after removal of the gut. Rats do not show sex differences in the pattern of elimination of the respective metabolites of the two herbicides. The rates of elimination of (14)C from the two compounds in the 24hr. and 48hr. urines are not significantly different (P >0.05) from one another. 2. After oral administration to dogs, 85.9-106.1% of (14)C from [(14)C]Prefix is excreted, 66.6-80.9% in the urine, and 86.8-92.5% of (14)C from 2,6-dichlorobenzo[(14)C]nitrile is excreted, 60.0-70.1% in the urine. Dogs do not show sex differences in the pattern of eliminating the metabolites of either Prefix or 2,6-dichlorobenzonitrile. 3. Dogs and rats do not show species differences in the patterns of elimination of the two herbicides. 4. Prefix and 2,6-dichlorobenzonitrile are completely metabolized; unchanged Prefix and 2,6-dichlorobenzonitrile are absent from the urine and faeces, and from the carcasses when elimination is complete. In the hydrolysed urine of rats dosed with either [(14)C]Prefix or 2,6-dichlorobenzo[(14)C]nitrile, 2,6-dichloro-3-hydroxybenzonitrile accounts for approx. 42% of the (14)C, a further 10-11% is accounted for by 2,6-dichlorobenzamide, 2,6-dichlorobenzoic acid, 2,6-dichloro-3- and -4-hydroxybenzoic acid and 2,6-dichloro-4-hydroxybenzonitrile collectively, and 25-30% by six polar constituents, of which two are sulphur-containing amino acids. 5. In the unhydrolysed urines of rats dosed with either [(14)C]Prefix or 2,6-dichlorobenzo[(14)C]nitrile, there are present free 2,6-dichloro-3- and -4-hydroxybenzonitrile, their glucuronide conjugates, ester glucuronides of the principal aromatic acids that are present in the hydrolysed urines, and two sulphur-containing metabolites analogous to mercapturic acids or premercapturic acids. 6. Prefix is thus extensively transformed into 2,6-dichlorobenzonitrile: R.CS.NH(2)-->R.CN+H(2)S, where R=C(6)H(3)Cl(2). However, the competitive reaction: R.CS.NH(2)+H(2)O-->R.CO.NH(2)+H(2)S takes place to a very limited extent.

摘要

给大鼠单次口服[(14)C]Prefix或2,6-二氯苯[(14)C]腈后，4天内几乎可完全消除：[(14)C]Prefix中84.8 - 100.5%的(14)C被排泄，其中67.3 - 79.7%经尿液排泄；2,6-二氯苯[(14)C]腈中85.8 - 97.2%的(14)C被排泄，其中72.3 - 80.7%经尿液排泄。去除肠道后，[(14)C]Prefix剂量的0.37±0.03%和2,6-二氯苯[(14)C]腈剂量的0.25±0.03%存在于 carcass 加内脏中。大鼠在两种除草剂各自代谢物的消除模式上无性别差异。两种化合物在24小时和48小时尿液中(14)C的消除率彼此无显著差异(P>0.05)。2. 给狗口服后，[(14)C]Prefix中85.9 - 106.1%的(14)C被排泄，其中66.6 - 80.9%经尿液排泄；2,6-二氯苯[(14)C]腈中86.8 - 92.5%的(14)C被排泄，其中60.0 - 70.1%经尿液排泄。狗在消除Prefix或2,6-二氯苯腈代谢物的模式上无性别差异。3. 狗和大鼠在两种除草剂的消除模式上无物种差异。4. Prefix和2,6-二氯苯腈完全代谢；尿液、粪便以及消除完成后的 carcass 中均不存在未变化的Prefix和2,6-二氯苯腈。在给[(14)C]Prefix或2,6-二氯苯[(14)C]腈的大鼠水解尿液中，2,6-二氯-3-羟基苯腈约占(14)C的42%，另外10 - 11%由2,6-二氯苯甲酰胺、2,6-二氯苯甲酸、2,6-二氯-3-和-4-羟基苯甲酸以及2,6-二氯-4-羟基苯腈共同占比，还有25 - 30%由六种极性成分占比，其中两种是含硫氨基酸。5. 在给[(14)C]Prefix或2,6-二氯苯[(14)C]腈的大鼠未水解尿液中，存在游离的2,6-二氯-3-和-4-羟基苯腈、它们的葡萄糖醛酸共轭物、水解尿液中存在的主要芳香酸的酯葡萄糖醛酸，以及两种类似于硫醚氨酸或前硫醚氨酸的含硫代谢物。6. 因此，Prefix广泛转化为2,6-二氯苯腈：R.CS.NH(2)-->R.CN + H(2)S，其中R = C(6)H(3)Cl(2)。然而，竞争反应：R.CS.NH(2)+H(2)O-->R.CO.NH(2)+H(2)S发生程度非常有限。