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Pharmacokinetics of Liposome-Encapsulated Meglumine Antimonate after Intramuscular and Subcutaneous Administration in Dogs

Controlling canine leishmaniasis may reduce the incidence of human leishmaniasis, which affect immunocompromised persons, especially those with human immunodeficiency virus infection. Thus, the pharmacokinetics of liposome-encapsulated meglumine antimonate (LMA) in dogs was studied after intramuscular (IM) and subcutaneous (SC) administration. Serum concentration-time data for both forms of administration were best described by a triexponential open model. The absorption phase showed statistically significant differences between IM and SC administrations (K01_IM = 0.046/min, K01_SC = 0.025/min). The first phase of decrease of plasma concentrations showed a longer half-life for SC than for IM administration, with the delay being caused by the slow absorption process after SC injection. Mean terminal phase half-lives after administration of IM and SC were 904.1 min and 637.4 min, respectively. Peak plasma concentrations after administration of IM (C_max = 43.8 µg/ml) and SC (C_max = 24.9 µg/ml) were detected at 42.8 min and 79.8 min, respectively. Urinary excretion of antimony for both routes surpassed 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 formulation suggest that for treating canine leishmaniasis, it would be more advisable to inject LMA intramuscularly if we assume that the significantly higher Cmax observed after IM administration is more relevant to dog's clinical outcome than is maintenance of concentrations over longer periods.