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 rand omly allocated into 4 treatment groups of 6 dogs each: oral (PO) UMF-078. P O 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 give n twice a day for 3 days to the 3 groups of treated dogs. Oral absorption i s rapid compared with IM dosing; the absorption half-life (K-10-HL) for the IM treatment is approximately 14 hr compared with 1 and 3 hr for the PO re gimen of salt and free base forms, respectively. The elimination half-lives (K-10-HL) Tur the PO regimens are 13 and 15 hr for the salt and free base forms, respectively. Because of sustained absorption following IM dosing, t he K-10-HL is prolonged. In contrast to oral administration, IM dosing of U MF-078 provides sustained, relatively low plasma drug levels, with good tol erance and efficacy.