Development of New Derivatives of Primaquine by Association with Lysosomotropic Carriers

Overview

Journal Bull World Health Organ

Specialty Public Health

Date 1981 Jan 1

PMID 6976852

Citations 12

Authors

A U Trouet

P Pirson

R Steiger

M Masquelier

R Baurain

J Gillet

Affiliations

Soon will be listed here.

Abstract

On the basis of the drug-carrier concept of chemotherapy, we entrapped primaquine in liposomes, and linked it to an amino acid (leucine), and to peptides (alanyl-leucine and alanyl-leucyl-alanyl-leucyl) as intermediate steps in the synthesis of covalent primaquine-glycoprotein conjugates that would be selectively recognized by hepatocytes.The therapeutic activity of these compounds was tested in mice infected with sporozoites of Plasmodium berghei. Causal prophylatic cures were obtained after a single intravenous injection of primaquine-liposomes (60-70 mg of primaquine/kg of bodyweight) and lower doses (35 mg of primaquine/kg of bodyweight) of ala-leu-primaquine and ala-leu-ala-leu-primaquine.The administration of such high doses was only possible as a result of the decreased toxicity of primaquine when entrapped in liposomes and confirms the validity of the drug-carrier concept for the treatment of malarial infections. The improved chemotherapeutic index of ala-leu-primaquine and ala-leu-ala-leu-primaquine resulted from their decreased toxicity and increased chemotherapeutic activity. These peptide derivatives are probably acting as pro-drugs of primaquine.

Citing Articles

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