Pharmacokinetics and dose proportionality of oral moxidectin in beagle dogs

Purpose . To study the pharmacokinetics and dose proportionality of moxidectin in beagle dogs experimentally infected with the filarial parasite Brugia pahangi , and to evaluate and compare the results obtained from population pharmacokinetic analysis and individual compartmental analysis. Method . Thirty‐six infected dogs were selected and randomly allocated into six treatment groups of six dogs each. Doses of 250 or 1000μg/kg were given orally. The plasma drug concentration–time data were analyzed by population compartmental and individual compartmental methods. Results . The best pharmacokinetic model was a two‐compartment model with first‐order absorption. According to the results obtained from population compartmental analysis, moxidectin is a low clearance drug with a relatively high volume of distribution, resulting in a mean terminal half‐life of 458 h. Absorption was rapid with a mean absorption half‐life of 0.6 h and T max of 2.75 h. Significant weight effect was found on Vc. These results were compared with results obtained from individual compartmental approach. A statistically significant ( p <0.01) gender difference in T1/2β was observed with the 250 μg/kg dose, and a trend was observed with a greater T1/2β in females at the 1000μg/kg dose. No gender effect on other pharmacokinetic parameters was found. Conclusions . A pronounced distribution phase was observed and there was a significant weight effect on Vc. Dose proportionality of moxidectin was assessed by comparing the AUC (0‐last determination) values for 250 and 1000μg/kg. The pharmacokinetics are independent of dose over this dose range. Copyright © 2002 John Wiley & Sons, Ltd.