Pharmacokinetics, urinary excretion and plasma protein binding of 2,3-butanedione monoxime in goats

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 μg ml−1. The pharmacokinetic parameters were determined by employing two-compartment open model. The t1/2α, t1/2β, 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.