TOXICITY PROFILE OF PARENTERAL ARTESUNATE FOLLOWING SUBACUTE TREATMENT
IN RATS AND DOGS
Abstract
OBJECTIVES The objectives of these studies were to investigate the
toxicity, safety and toxicokinetics of single and multiple doses of
artesunate for injection in rats and dogs. METHODS Sprague-Dawley rats
and Beagle dogs were treated intravenously or intramuscularly for 28
consecutive days with doses of up to 30 mg/kg artesunate, evaluating
toxicity, kinetics, genotoxicity, and cardiovascular and central nervous
safety parameters after single and 4-week repeated administrations.
Furthermore, respiratory parameters were evaluated after a single
intravenous administration in rats. RESULTS Artesunate was well
tolerated with no mortality and only minor effects on clinical pathology
parameters. Following repeated intramuscular administration, local
reactions at the injection site became evident. Signs of regenerative
anaemia were evident in both rats and dogs and are attributed to the
pharmacological effect of artesunate (effective against blood stages of
malaria parasites). No severe toxicity or any effects on safety measures
were noticed. CONCLUSIONS The results obtained in these studies support
the safe use of intravenous and intramuscular artesunate for a period
beyond the commonly used three (to maximum seven) days in humans.
Cardiovascular, central nervous and respiratory safety measures indicate
no risk at clinically used doses.