Moxidectin: Metabolic Fate and Blood Pharmacokinetics of 14C-Labeled Moxidectin in Horses

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• 作者：Jalees Afzal ; Alison B. Burke ; Peter L. Batten ; Roger L. DeLay ; and Phillip Miller
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：1997
• 出版时间：September 1997
• 年：1997
• 卷：45
• 期：9
• 页码：3627 - 3633
• 全文大小：211K
• 年卷期：v.45,no.9(September 1997)
• ISSN：1520-5118

文摘

Serum and whole blood pharmacokinetics of moxidectin and excretion andbiotransformation inedible tissues and excreta have been evaluated in the horse at a doselevel of 0.4 mg/kg of bodyweight. Three animals were orally dosed with¹⁴C-labeled moxidectin, formulated as a gel.Totalradioactive residues (TRR) were determined in whole blood and in serumcollected at selectedintervals through 168 h. Sera samples were also assayed for intactmoxidectin. At 168 h, animalswere sacrificed and TRR determined in edible tissues, namely muscle,liver, kidney, and fat. Themean terminal elimination half-lives for total radioactivity and parentin serum were 154 ± 26 and82 ± 23 h, respectively. Fecal excretion was the mainelimination pathway, accounting for 77% ofthe administered dose by 168 h. Although minor metabolites werenoted, intact parent was themajor component in tissues and excreta. Similarly, three animalswere intravenously (iv) dosedwith ¹⁴C-labeled moxidectin, formulated as an aqueousinjectable solution. The terminal eliminationhalf-lives for total radioactivity and intact parent in serum were 128± 14 and 81 ± 18 h, respectively.On the basis of a comparison of intact parent area under theconcentration/time (AUC) values of4.55 and 11.4 g·h/g following oral and iv doses, respectively, anoral bioavailability of approximately40% was estimated.Keywords: Moxidectin; blood pharmacokinetics; horses;bioavailability