Publication: Assessment of the neurotoxicity of parenteral artemisinin derivatives in mice
Issued Date
1998-01-01
Resource Type
ISSN
00029637
Other identifier(s)
2-s2.0-0031785145
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Tropical Medicine and Hygiene. Vol.59, No.4 (1998), 519-522
Suggested Citation
Apichart Nontprasert, Marika Nosten-Bertrand, Sasithon Pukrittayakamee, Sirivan Vanijanonta, Brian J. Angus, Nicholas J. White Assessment of the neurotoxicity of parenteral artemisinin derivatives in mice. American Journal of Tropical Medicine and Hygiene. Vol.59, No.4 (1998), 519-522. doi:10.4269/ajtmh.1998.59.519 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/18405
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Assessment of the neurotoxicity of parenteral artemisinin derivatives in mice
Other Contributor(s)
Abstract
In all experimental mammals tested (rats, dogs, primates), intramuscular injections of the oil-soluble antimalarial artemisinin derivatives artemether and arteether have produced an unusual pattern of selective damage to brain stem centers predominantly involved in auditory processing and vestibular reflexes. Artesunate, the most widely used of these compounds, is a water soluble hemisuccinate derivative given parenterally either by intravenous or intramuscular injection. The neurotoxic potential of parenteral artesunate and artemether was compared in a murine model. Adult Swiss albino mice were assigned randomly to 28-day regimens of intramuscular artemether or artesunate in doses ranging from 30 to 100 mg/kg/day. At 30 mg/kg/day, no abnormalities were detected with either drug. At 50 mg/kg/day, abnormalities were observed in six of 12 artemether recipients and two of 12 artesunate recipients. These were reversible in all but one (artemether) mouse. At 100 mg/kg/day, eight of 36 artemether recipients, two of 36 artesunate recipients, and one of 18 control mice died. All but four surviving mice in the artemether group (86%) showed obvious and usually irreversible abnormalities of balance and equilibrium, whereas only four artesunate recipients (11%) exhibited abnormalities, and these were reversible in each case (P < 0.001). At this dose the relative risk (95% confidence interval) for death or disability was 5.3 (2.6-11.2) for artemether recipients. Intramuscular artemether is significantly more neurotoxic than intramuscular artesunate in this murine model.