Abstract :
Inhibition of acetylcholinesterase in the central and peripheral nervous system is the
basic mechanism of action of organophosphate nerve agents. Of the several phosphorylated
acetylcholinesterase reactivators available, 2,3-butanedione monoxime has been
reported to successfully reactive acetylcholinesterase enzyme in central nervous system
of domestic animals severely poisoned with organophosphorus insecticides. The blood
levels of cholinesterase reactivator 2,3-butanedione monoxime (common name diacetyl
monoxime; abbreviated as DAM) were determined in goats following single dose intravenous
administration @ 30 mg/kg body weight injected as 6% solution. Blood and urine
samples were collected at different predetermined time intervals and DAM was analysed
by colorimetric method with the minimum detection of 1.0 gml−1. The pharmacokinetic
parameters were determined by employing two-compartment open model. The t1/2 , t1/2 ,
Vdarea and ClB were calculated to be 6.02±2.65 min, 103.3±8.54 min, 548.86±96.53 ml/kg
and 3.64±0.41 ml/kg/min, respectively. Approximately 10.44% of the total administered
dose was eliminated in urine within 24 h. The plasma protein binding was estimated by
equilibrium dialysis technique. The in vitro plasma protein binding of DAM was 54.4%.
Based on these data, a satisfactory intravenous dosage regimen of DAM in goats would
be 28 mg/kg body weight repeated at 6 h intervals.
