Pharmacokinetics, urinary excretion and plasma protein binding of pralidoxime in goats

The blood levels of cholinesterase reactivator pralidoxime (2-PAM) were determined in goats following single dose intravenous administration @30 mg/kg body weight injected as 6% freshly prepared solution. Blood and urine samples were collected at different predetermined time intervals and 2-PAM was analysed by spectrometric method with the minimum detection of 1.0 mu g ml(-1). The peak plasma concentration was 49.52 +/- 3.99 mu g ml(-1) at 2 min post administration which rapidly declined to 15.53 +/- 2.11 mu g ml(-1) at 10 min. Thereafter, it gradually disappeared to 1.33 +/- 0.41 mu g ml(-1) at 1.5 h. The pharmacokinetic parameters were determined by employing two-compartment open model. The t(1/2 alpha), t(1/2 beta). Vd(area) and Cl(B) were calculated to be 1.68 +/- 0.35 min, 21.17 +/- 1.65 min, 1277.95 +/- 195.67 ml/kg and 41.17 +/- 3.66 ml/kg/min, respectively. Approximately 52% 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 2-PAM was 64.7%. Based on these data, a satisfactory intravenous dosage regimen of 2-PAM in goats would be 38 mg/kg body weight repeated at hourly intervals. (C) 2010 Elsevier B.V. All rights reserved.