Karadzovska D, Seewald W, Browning A, Smal M, Bouvier J, Giraudel J M
Novartis Animal Health Australasia Pty Limited, Yarrandoo R & D Centre, New South Wales, Australia.
J Vet Pharmacol Ther. 2009 Aug;32(4):359-67. doi: 10.1111/j.1365-2885.2008.01052.x.
The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg x h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg x h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally (AUC((0-infinity)) oral/AUC((0-infinity)) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.
在绵羊静脉注射（i.v.）和口服给药后，对新型氨基乙腈衍生物（AAD）莫能菌素及其砜代谢物莫能菌素砜的药代动力学特性进行了研究。无论给药途径如何，给药4小时后砜代谢物迅速形成并在含量上超过莫能菌素。莫能菌素的稳态分布容积、全身清除率和平均驻留时间分别为7.4 L/kg、1.49 L/(kg·h)和4.9小时，莫能菌素砜分别为31.2 L/kg、0.28 L/(kg·h)和111小时。莫能菌素的总体生物利用度为31%，但研究表明，无论莫能菌素是静脉注射还是口服，产生的莫能菌素砜量大致相同（莫能菌素砜的口服AUC((0 - ∞))/静脉注射AUC((0 - ∞))为94%），就所产生的砜代谢物量而言，口服给药是莫能菌素非常有效的给药途径。由于莫能菌素砜是莫能菌素给药后绵羊血液中存在的主要化学物质，并且它也是一种活性代谢物，其药代动力学特性对于解释未来的残留和疗效研究至关重要。总体而言，这些药代动力学数据有助于评估莫能菌素作为绵羊口服驱虫药的效果。
