Pharmacokinetics, urinary excretion and plasma protein binding of 2,3-butanedione monoxime in goats
2010
Rahal, Anu | Malik, J.K.
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 @ 30mg/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 1.0μgml⁻¹. The pharmacokinetic parameters were determined by employing two-compartment open model. The t ₁/₂α, t ₁/₂β, Vdarea and ClB were calculated to be 6.02±2.65min, 103.3±8.54min, 548.86±96.53ml/kg and 3.64±0.41ml/kg/min, respectively. Approximately 10.44% of the total administered dose was eliminated in urine within 24h. 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 28mg/kg body weight repeated at 6h intervals.
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