Disposition of antimony after the administration of N-methylglucamine antimoniate to dogs.
A study was carried out in dogs to define the pharmacokinetic profile of antimony and to define a better therapeutic protocol for the treatment of canine leishmaniasis. Six healthy beagle dogs received 100 mg/kg of N-methylglucamine antimoniate containing 27.2 per cent of antimony intravenously, intramuscularly and subcutaneously. After intravenous administration the plasma concentration of antimony decreased rapidly and after 240 minutes it was lower than the ED50 values suggested for Leishmania donovani. The pharmacokinetic parameters and bioavailability of antimony were calculated after each route of administration in each dog. The curves of plasma concentrations vs time were best described by a triexponential open model with a mean (sd) half life t1/2 alpha of 9.4 (4.4) min, a t1/2 beta of 45.3 (4.5) min and a t1/2 gamma of 618.0 (93.5) min. The mean volume of distribution at steady state was 0.25 (0.03) litres/kg and the total body clearance was 0.25 (0.04) litres/h/kg. The peak plasma concentration (Cmax) after intramuscular administration was 27.2 (3.1) micrograms/ml, and after subcutaneous administration it was 25.5 (4.5) micrograms/ml; they were reached after 73.6 (11.9) min and 85.6 (11.3) min, respectively. The bioavailabilities after intramuscular and subcutaneous administration were 91.7 (7.1) and 92.2 (7.1) per cent, respectively. More than 80 per cent of the antimony was excreted in the urine in the first nine hours.
Valladares
J E
JE
Divisió de Farmacologia, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Alberola
J
J
Esteban
M
M
Arboix
M
M
D000818:Animals; D000965:Antimony / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism; D004285:Dogs / Q000378:metabolism*; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007279:Injections, Subcutaneous / Q000662:veterinary; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony