PHARMACOKINETICS OF LIPOSOME-ENCAPSULATED MEGLUMINE ANTIMONATE AFTER INTRAMUSCULAR AND SUBCUTANEOUS ADMINISTRATION IN DOGS

Controlling canine leishmaniasis may reduce the incidence of human lei shmaniasis, which affect immunocompromised persons, especially those w ith human immunodeficiency virus infection. Thus, the pharmacokinetics of liposome-encapsulated meglumine antimonate (LMA) in dogs was studi ed after intramuscular (IM) and subcutaneous (SC) administration. Seru m concentration-time data for both forms of administration were best d escribed by a triexponential open model. The absorption phase showed s tatistically significant differences between IM and SC administrations (K0(IM) = 0.046/min, K01(SC) = 0.025/min). The first phase of decreas e of plasma concentrations showed a longer half-life for SC than for I M administration, with the delay being caused by the slow absorption p rocess after SC injection. Mean terminal phase half-lives after admini stration of IM and SC were 904.1 min and 637.4 min, respectively. Peak plasma concentrations after-administration of IM (C-max = 43.8 mu g/m l) and SC (C-max = 24.9 mu g/ml) were detected at 42.8 min and 79.8 mi n, respectively. Urinary excretion of antimony for both routes surpass ed 80% during the first 6 hr, with the rest of the drug being excreted slowly over the following 18 hr The results obtained with this formul ation suggest that for treating canine leishmaniasis, it would be more advisable to inject LMA intramuscularly if we assume that the signifi cantly higher Cmax observed after IM administration is more relevant t o dog's clinical outcome than is maintenance of concentrations over lo nger periods.