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, 30 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 parameters, an appropriate dosage regimen of 2-PAM in B. bubalis was calculated. There was no significant difference between plasma levels and pharmacokinetic parameters of 2-PAM in the two groups of animals, given 2-PAM alone and in conjunction with atropine. The peak plasma concentration of 2-PAM at 1 min was in the range of 189.5-196.6 microg/mL which declined to 9.22-9.98 microg/mL at 4 h. The values of elimination half-life, Vd(area) and total body clearance were 2.41-2.67 h, 0.77-0.95 L/kg and 227.5-245.7 mL/kg/h, respectively. The binding capacity of 2-PAM to plasma proteins of fenitrothion-intoxicated 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. Approximately 63% of 2-PAM was bound with plasma proteins. In the treatment of organophosphate insecticide (OPI) toxicity in B. bubalis, an appropriate i.v. dosage regimen of 2-PAM in conjunction with atropine would be 18 mg/kg followed by 15 mg/kg at 4 h interval.
Srivastava
A K
AK
Department of Pharmacology & Toxicology, College of Veterinary Science, Punjab Agricultural University, Ludhiana, India.
Malik
J K
JK
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001285:Atropine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002020:Buffaloes; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000188:drug therapy / Q000662:veterinary; D005278:Fenitrothion / Q000506:poisoning*; D006207:Half-Life; D007275:Injections, Intravenous; D007306:Insecticides / Q000506:poisoning*; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010091:Oximes / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007306:Insecticides; D018727:Muscarinic Antagonists; D010091:Oximes; D001285:Atropine; C060977:pyridine-2-aldoxime; D005278:Fenitrothion