Efficacy of ivermectin against Strongyloides stercoralis infection in jirds (Meriones unguiculatus).
The activity and distribution of ivermectin (IVM), a broad spectrum anthelmintic for various nematodes and arthropods, was tested against Strongyloides stercoralis infection in the jird (Meriones unguiculatus.) The pattern of IVM concentration in the serum of jirds after either low- (200 microg/kg) or high-dose (1000 microg/kg) treatment by intraperitoneal injection showed a typical single-peak profile with the maximum drug levels detected at 1 h followed by a rapid decline to undetectable values by 48 h posttreatment. With equivalent IVM doses, the serum levels in male jirds were significantly higher than those observed in female jirds at 1 and 12 h posttreatment (P < 0.05). Low-dose IVM treatment of either male or female jirds, in comparison with that of the respective control groups, produced no observable effect on the adult worm burden or the parasite fecundity. The curative dose for S. stercoralis in both sexes of animals was achieved when using the high dose of 1000 microg/kg of IVM. The area under the curve calculated from the serum-concentration profiles in males was significantly higher than that for females after the high-dose treatment of IVM (P < 0.05). By low-dose treatment, a significantly lower adult worm burden was observed in males compared with that in females (P < 0.05), and this difference correlated with the higher serum levels of IVM in male animals. The distribution of IVM in the jird after high-dose treatment was characterized by initial appearances at 1 h of maximum levels of the drug in the serum and intestinal content. The maximum level in the feces was reached at 12 h posttreatment and rapidly declined thereafter. The level in the intestinal tissue was comparatively much lower than that in the intestinal content and the feces. The half-life of IVM in the intestinal content (49.5 h) was longer than those in the serum, feces, and intestinal tissue (6.53-13.07 h). Analyses of the relationship between the peak serum IVM occurring at 1 h posttreatment and the adult worm recovery revealed that the minimal serum concentration associated with clearance of the adult worm from the jird was approximately 0.65 microg/ml. The jird-S. stercoralis model has not only made studies on various aspects of parasite biology possible, but also provided an in vivo system to examine the efficacy as well as the mode of action of IVM against this intestinal nematode.
Sithithaworn
P
P
Department of Parasitology, Faculty of Medicine, Khon Kaen University, Thailand.
Fujimaki
Y
Y
Mitsui
Y
Y
Prasanthong
R
R
Yutanawiboonchai
W
W
Aoki
Y
Y
D000818:Animals; D000969:Antinematodal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005260:Female; D005298:Fertility / Q000187:drug effects; D005766:Gastrointestinal Contents / Q000737:chemistry; D005849:Gerbillinae; D006207:Half-Life; D007413:Intestinal Mucosa / Q000378:metabolism; D007559:Ivermectin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D012727:Sex Characteristics; D017171:Strongyloides stercoralis / Q000187:drug effects* / Q000502:physiology; D013322:Strongyloidiasis / Q000188:drug therapy* / Q000469:parasitology; D014018:Tissue Distribution
D000969:Antinematodal Agents; D007559:Ivermectin