Pharmacokinetics of UMF-078, a candidate antifilarial drug, in infected dogs.
The pharmacokinetics of the filaricidal benzimidazole compounds UMF-078 and UMF-289 were evaluated in beagle dogs experimentally infected with Brugia pahangi. Twenty-four infected microfilaremic beagles were selected and randomly allocated into 4 treatment groups of 6 dogs each: oral (PO) UMF-078, PO UMF-289 (the HCl salt form of UMF-078), intramuscular (IM) UMF-078, and untreated controls. Equivalent doses of 50 mg/kg of the free base were given twice a day for 3 days to the 3 groups of treated dogs. Oral absorption is rapid compared with IM dosing; the absorption half-life (K01-HL) for the IM treatment is approximately 14 hr compared with 1 and 2 hr for the PO regimen of salt and free base forms, respectively. The elimination half-lives (K10-HL) for the PO regimens are 13 and 15 hr for the salt and free base forms, respectively. Because of sustained absorption following IM dosing, the K10-HL is prolonged. In contrast to oral administration, IM dosing of UMF-078 provides sustained, relatively low plasma drug levels, with good tolerance and efficacy.
Theplertboon
R
R
College of Pharmacy, University of Iowa, Iowa City 52242, USA.
Fleckenstein
L
L
Dzimianski
M T
MT
McCall
J W
JW
D000284:Administration, Oral; D000818:Animals; D000969:Antinematodal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D017179:Brugia pahangi / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D005368:Filariasis / Q000188:drug therapy* / Q000378:metabolism; D006207:Half-Life; D007273:Injections, Intramuscular; D008297:Male; D008463:Mebendazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011897:Random Allocation
D000969:Antinematodal Agents; C089375:UMF 078; D008463:Mebendazole; C018945:flubendazole