Pharmacokinetics and dosage regimen of 2-pyridine aldoxime in Bubalus bubalis intoxicated with fenitrothion

In the present study, the pharmacokinetics of 2-pyridine aldoxime (2-PAM, 3 0 mg/kg, i.v.) alone and in conjunction with atropine (0.3 mg/kg; 1/4 i.v., 3/4 i.m.) was investigated in 10 Bubalus bubalis intoxicated with a single oral lethal dose of fenitrothion (435 mg/kg). Based on the kinetic paramet ers, an appropriate dosage regimen of 2-PAM in B. bubalis was calculated. T here was no significant difference between plasma levels and pharmacokineti c parameters of 2-PAM in the two groups of animals, given 2-PAM alone and i n conjunction with atropine. The peak plasma concentration of 2-PAM at 1 mi n was in the range of 189.5-196.6 mug/mL, which declined to 9.22-9.98 mug/m L at 4 h. The values of elimination half-life, V-d(area) and total body cle arance were 2.41-2.67 h, 0.77-0.95 L/kg and 227.5-245.7 mL/kg/h, respective ly. The binding capacity of 2-PAM to plasma proteins of fenitrothion-intoxi cated buffalo calves and dissociation rate constant of protein drug complex were 0.015 x 10(-6) mol/g and 2.367 x 10(-6) mol, respectively. Approximat ely 63% of 2-PAM was bound with plasma proteins. In the treatment of organo phosphate insecticide (OPI) toxicity in B. bubalis, an appropriate i.v. dos age regimen of 2-PAM in conjunction with atropine would be 18 mg/kg followe d by 15 mg/kg at 4 h interval.