title: The effect of sheep breed, age, and gender on the pharmacokinetics and efficacy of monepantel, an amino-acetonitrile derivative.
abstract: This analysis investigated the influence of breed and gender on the pharmacokinetics of monepantel, and influence of breed, age, and gender on its efficacy against gastrointestinal nematodes of sheep. In a comparison of pharmacokinetic profiles from two studies, Merino lambs had significantly greater maximum concentrations of monepantel and monepantel sulfone, and faster times to reach these concentrations than Dorset cross lambs. Males had a statistically greater area under the curve (0-504 h) than females for monepantel sulfone. The biological relevance of these relatively small differences is unclear because efficacy was not evaluated in these studies. For efficacy, a breed effect existed for some nematodes when sheep were treated at a sub-optimum dose (1.25 mg/kg). There were no gender effects between sheep infected with adult parasites and treated at 1.25 mg/kg but there were differences between females and males treated at this dose when infected with fourth-stage larvae of Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis, and Cooperia curticei. There were no breed or gender differences for sheep treated at the recommended dose (2.5 mg/kg). There was a potential trend for declining efficacy with increasing animal age for fourth-stage Trichostrongylus axei. This analysis demonstrated that, similarly to what is observed with other anthelmintics, the pharmacokinetics and efficacy of monepantel can vary with factors like breed, age, and gender. Identifying these covariates is important for understanding inter-individual variability in drug response. While further investigation is warranted, correctly treating sheep at the recommended dose of 2.5 mg/kg appears to mitigate any associated risk.
authors.affiliation: Novartis Animal Health Australasia Pty Limited, Yarrandoo R & D Centre, 245 Western Road, Kemps Creek, New South Wales 2178, Australia. barry.hosking@novartis.com
authors.forename: Barry C
authors.initials: BC
authors.lastname: Hosking
authors.forename: Ronald
authors.initials: R
authors.lastname: Kaminsky
authors.forename: Heinz
authors.initials: H
authors.lastname: Sager
authors.forename: Daniela
authors.initials: D
authors.lastname: Karadzovska
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seewald
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Giraudel
authors.forename: Jozef
authors.initials: J
authors.lastname: Vercruysse
mesh_terms: D000367:Age Factors; D000607:Aminoacetonitrile / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006374:Helminthiasis, Animal / Q000188:drug therapy*; D008297:Male; D010375:Pedigree; D012737:Sex Factors; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy*
chemical_list: D000871:Anthelmintics; D000607:Aminoacetonitrile; C533978:monepantel