title: Pharmacokinetics of experimental pentavalent antimony after intramuscular administration in adult volunteers.
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.
authors.affiliation: University of The Andes, Faculty of Medicine, Valera School of Medicine, Laboratory of Pharmacology, Valera, Venezuela ; University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
authors.forename: Laura
authors.initials: L
authors.lastname: Vásquez
authors.affiliation: University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
authors.forename: José V
authors.initials: JV
authors.lastname: Scorza Dagert
authors.affiliation: University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
authors.forename: José V
authors.initials: JV
authors.lastname: Scorza
authors.affiliation: University of The Andes, Faculty of Medicine, Valera School of Medicine, Laboratory of Pharmacology, Valera, Venezuela.
authors.forename: Nelson
authors.initials: N
authors.lastname: Vicuña-Fernández
authors.affiliation: University of The Andes, Faculty of Sciences, Laboratory of MolecularSpectroscopy, La Hechicera, Venezuela.
authors.forename: Yaneira Petit
authors.initials: YP
authors.lastname: de Peña
authors.affiliation: University of The Andes, Faculty of Sciences, Laboratory of MolecularSpectroscopy, La Hechicera, Venezuela.
authors.forename: Sabrina
authors.initials: S
authors.lastname: López
authors.affiliation: University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
authors.forename: Herminia
authors.initials: H
authors.lastname: Bendezú
authors.affiliation: University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
authors.forename: Elina
authors.initials: E
authors.lastname: Rojas
authors.affiliation: University of The Andes, Faculty of Medicine, Valera School of Medicine, Laboratory of Pharmacology, Valera, Venezuela.
authors.forename: Libia
authors.initials: L
authors.lastname: Vásquez
authors.affiliation: University of The Andes, Center of Parasitological Investigations, José Witremundo Torrealba, NURR, Trujillo, Venezuela.
authors.forename: Belén
authors.initials: B
authors.lastname: Pérez
keywords: Ulamina; antileishmania drugs; antimony; humans; pharmacokinetic