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Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2006 May;67(3):193–203. doi: 10.1016/j.curtheres.2006.06.005

Pharmacokinetics of experimental pentavalent antimony after intramuscular administration in adult volunteers*

Laura Vásquez 1,2,**, José V Scorza Dagert 2, José V Scorza 2, Nelson Vicuña-Fernández 1, Yaneira Petit de Peña 3, Sabrina López 3, Herminia Bendezú 2, Elina Rojas 2, Libia Vásquez 1, Belén Pérez 2
PMCID: PMC3965980  PMID: 24678095

Abstract

Background:

Pentavalent antimony (SbV) has demonstrated therapeuticeffectiveness against clinical manifestations of leishmaniasis, an infection caused by Leishmania, a genus of flagellate protozoa comprising parasites of worldwide distribution. Approximately 1.8 million new cases are reported annually.

Objective:

The aim of this study was to assess the pharmacokinetics of the investigational generic SbV, Ulamina (pentachloride of antimony + N-methylglucamine), in healthy adult volunteers.

Methods:

In this study, SbV was administered IM as a single 5-mg/kg dose.Blood samples were collected at 0.25, 0.75, 1, 2, 4, 8, 12, and 24 hours after administration; urine samples were collected at 6-hour intervals during the 24-hour postadministration period. Determination of trivalent antimony, SbV, and total antimony concentrations in blood and urine samples was carried out using atomic absorption spectrometry. Clinical history was reviewed and the subjects were monitored before and after administration of SbV using physical examination, weight, and hepatic- and renal-function studies. The pharmacokinetic parameters calculated were Cmax, Tmax, absorption constant (Ka), elimination constant (Kel), AUC2–24h, AUC0-∞, elimination phase (t½β), volume of distribution (Vd), and urinary excretion rate.

Results:

Five subjects (3 men, 2 women; mean age, 28 years [range, 18–34 years]) were included in the study. One hour after drug administration the following values were obtained: Cmax, 1.1 μg/mL; Tmax, 1.3 hours; Ka, 1.87 hours; Kel, 0.043 hours; AUC0–24h, 12.26 μg/mL · h; AUC0-∞, 19.84 μg/mL · h; t½β, 17.45 hours; Vd, 6.6 L/kg; and urinary excretion rate, 2.8 μg/h; these were mean values for the entire study group. The single dose was well tolerated by all subjects.

Conclusions:

The investigational generic SbV, Ulamina, was associated with linearelimination after IM administration of a single 5-mg/kg dose. A 2-compartment pharmacokinetic model was observed in these volunteers; the mean t½β, was 17.45 hours and the mean Vd was 6.6 L/kg.

Key words: pharmacokinetic, antimony, Ulamina, humans, antileishmania drugs

Full Text

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Footnotes

*

Some results contained in this manuscript were presented at the First International Congress ofTherapeutics 2005 & XVII Congress of the Latin American Association of Pharmacology, October 28, 2005. Caracas City, Venezuela.

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