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Pharmacokinetics, toxicities, and efficacies of sodium stibogluconate formulations after intravenous administration in animals

Nieto, J. and Alvar, J. and Mullen, A. and Carter, K.C. and Rodriguez, C. and San Andres, M.I. and San Andres, M.D. and Baillie, A.J. (2003) Pharmacokinetics, toxicities, and efficacies of sodium stibogluconate formulations after intravenous administration in animals. Antimicrobial Agents and Chemotherapy, 47 (9). pp. 2781-2787. ISSN 0066-4804

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Abstract

The pharmacokinetics and toxicities of free sodium stibogluconate (SSG) and two vesicular formulations of this drug (a nonionic surfactant vesicular formulation of SSG [SSG-NIV] and SSG-NIV-dextran) were determined after treatment with a single intravenous dose in healthy dogs and were related to their antileishmanial efficacies in mice. Analysis of the curves of the concentrations in plasma after intravenous administration of SSG and SSG-NIV in dogs showed that both formulations produced similar antimony (Sb) pharmacokinetics. In contrast, treatment with SSG-NIV-dextran significantly modified the pharmacokinetics of the drug. The elimination half-life was four times longer (280 min) than that observed after administration of SSG (71 min) (P = 0.01), and the volume of distribution at steady state (V-SS) was also increased (V-SS for SSG, 0.21 liters/kg; V-SS for SSG-NIV-dextran, 0.34 liters/kg [P = 0.02]), thus indicating that drug encapsulation favors the distribution of Sb into organs and increases its residence time in tissues. This would explain the superior antileishmanial efficacy of this formulation compared to those of the free drug in mice. No signs of toxicity were found in dogs after SSG and SSG-NIV administration. However, SSG-NIV-dextran treatment was associated with short-term toxicity, demonstrated by the development of chills and diarrhea, which cleared by 24 h postdosing, and hepatic dysfunction at 24 h postdosing (P < 0.05). The levels of all the biochemical parameters had returned to normal at 1 month postdosing. No signs of toxicity were observed in mice treated with all three formulations.

Item type: Article
ID code: 22831
Notes: Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.
Keywords: encapsulated meglumine antimonate, visceral leishmaniasis, canine leishmaniasis, amphotericin-b, balb/c mouse, dogs, complement, donovani, mice, disposition, Pharmacy and materia medica
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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    Depositing user: Strathprints Administrator
    Date Deposited: 07 Jul 2010 12:08
    Last modified: 04 Oct 2012 13:18
    URI: http://strathprints.strath.ac.uk/id/eprint/22831

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