Pharmacokinetics of experimental pentavalent antimony after intramuscular administration in adult volunteers

Laura Vásquez, José V. Scorza Dagert, José V. Scorza, Nelson Vicuña-Fernández, Yaneira Petit de Peña, Sabrina López, Herminia Bendezú, Elina Rojas, Libia Vásquez, Belén Pérez

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

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 (t1/2β), 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; t1/2β, 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 t1/2β, was 17.45 hours and the mean Vd was 6.6 L/kg. © 2006 Excerpta Medica, Inc.
Original languageEnglish
Pages (from-to)193-203
JournalCurrent Therapeutic Research
Volume67
DOIs
Publication statusPublished - 1 May 2006

Keywords

  • Ulamina
  • antileishmania drugs
  • antimony
  • humans
  • pharmacokinetic

Fingerprint Dive into the research topics of 'Pharmacokinetics of experimental pentavalent antimony after intramuscular administration in adult volunteers'. Together they form a unique fingerprint.

Cite this