title: Doramectin--a potent novel endectocide.
abstract: Doramectin, 25-cyclohexyl-5-O-demethyl-25-de(l-methylpropyl)avermectin A1a, was selected as the best of a series of novel avermectins prepared by mutational biosynthesis. The primary evaluation of its in vivo antiparasitic activity was carried out using a rat Trichostrongylus colubriformis model and a rabbit Psoroptes cuniculi model. In each case the new avermectin performed favourably relative to dihydroavermectin B1a (DHAVM), the major component of ivermectin. Doramectin was extensively evaluated in cattle using an experimental micelle formulation, proving highly effective in cattle infected with Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus when administered subcutaneously at 200 micrograms kg-1. The plasma pharmacokinetic characteristics of doramectin in cattle following intravenous administration revealed a plasma half-life of approximately 89 h. In the micelle formulation, doramectin administered subcutaneously at 400 micrograms kg-1 provided persistent activity against infection of cattle with C. oncophora and O. ostertagi for at least 8 and 12 days respectively.
authors.affiliation: Pfizer Central Research, Sandwich, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Goudie
authors.forename: N A
authors.initials: NA
authors.lastname: Evans
authors.forename: K A
authors.initials: KA
authors.lastname: Gration
authors.forename: B F
authors.initials: BF
authors.lastname: Bishop
authors.forename: S P
authors.initials: SP
authors.lastname: Gibson
authors.forename: K S
authors.initials: KS
authors.lastname: Holdom
authors.forename: B
authors.initials: B
authors.lastname: Kaye
authors.forename: S R
authors.initials: SR
authors.lastname: Wicks
authors.forename: D
authors.initials: D
authors.lastname: Lewis
authors.forename: A J
authors.initials: AJ
authors.lastname: Weatherley
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D007279:Injections, Subcutaneous / Q000662:veterinary; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007411:Intestinal Diseases, Parasitic / Q000188:drug therapy / Q000662:veterinary; D007559:Ivermectin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008823:Micelles; D008924:Mite Infestations / Q000188:drug therapy / Q000662:veterinary*; D008925:Mites; D009349:Nematode Infections / Q000188:drug therapy / Q000662:veterinary*; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014253:Trichostrongylosis / Q000188:drug therapy / Q000662:veterinary
chemical_list: D000871:Anthelmintics; D007306:Insecticides; D008823:Micelles; C022120:avermectin B(1)a; D007559:Ivermectin; C084101:doramectin