Toxicity of the antimalarial artemisinin and its dervatives

Publication type:
Journal article
Metadata:
Autoren
  • Thomas Efferth
  • Bernd Kaina
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000276814400002&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3109/10408441003610571
eISSN
1547-6898
Externe Identifier
  • Clarivate Analytics Document Solution ID: 585GZ
  • PubMed Identifier: 20158370
ISSN
1040-8444
Ausgabe der Veröffentlichung
5
Zeitschrift
CRITICAL REVIEWS IN TOXICOLOGY
Paginierung
405 - 421
Datum der Veröffentlichung
2010
Status
Published
Titel
Toxicity of the antimalarial artemisinin and its dervatives
Sub types
  • Review
Ausgabe der Zeitschrift
40

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Thomas Efferth
  • Bernd Kaina
DOI
10.3109/10408441003610571
eISSN
1547-6898
ISSN
1040-8444
Ausgabe der Veröffentlichung
5
Zeitschrift
Critical Reviews in Toxicology
Sprache
en
Online publication date
2010
Paginierung
405 - 421
Datum der Veröffentlichung
2010
Status
Published
Herausgeber
Informa UK Limited
Herausgeber URL
http://dx.doi.org/10.3109/10408441003610571
Datum der Datenerfassung
2020
Titel
Toxicity of the antimalarial artemisinin and its dervatives
Ausgabe der Zeitschrift
40

Data source: Crossref

Abstract
As long as no effective malaria vaccine is available, chemotherapy belongs to the most important weapons fighting malaria. One of the most promising new drug developments is the sesquiterpene artemisinin (ARS) and its derivatives, e.g., artemether, arteether, and sodium artesunate. Large clinical studies and meta-analyses did not show serious side effects, although proper monitoring of adverse effects in developing countries might not be a trivial task. There is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity. Therefore, a final and definitive statement on the safety of artemisinins still cannot be made. In contrast, animal experiments show considerable toxicity upon application of artemisinins. In the present review, the authors give a comprehensive overview on toxicity studies in cell culture and in animals (mice, rats, rabbits, dogs, monkeys) as well as on toxicity reported in human clinical trials. The authors emphasize the current knowledge on neurotoxicity, embryotoxicity, genotoxicity, hemato- and immunotoxicity, cardiotoxicity, nephrotoxicity, and allergic reactions. The lesson learned from animal and human studies is that long-term availability rather than short-term peak concentrations of artemisinins cause toxicity. Rapid elimination of artemisinins after oral intake represents a relatively safe route of administration compared to delayed drug release after intramuscular (i.m.) injection. This explains why considerable toxicities were found in the majority of animal experiments, but not in human studies. In addition, there are drug-related differences, i.e., intramuscular application of artemether or arteether, but not to artesunate, which is safe and gives good profiles after i.m. administration in severe malaria. Although there is no need to increase doses of artemisinins for uncomplicated malaria, this has to be taken into account for cerebellar involvement in severe malaria. It might also be important in determining dose limitations for treatment of other diseases such as cancer.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany. efferth@uni-manz.de
Autoren
DOI
10.3109/10408441003610571
eISSN
1547-6898
Externe Identifier
  • PubMed Identifier: 20158370
Open access
false
ISSN
1040-8444
Ausgabe der Veröffentlichung
5
Zeitschrift
Critical reviews in toxicology
Schlüsselwörter
  • Animals
  • Dogs
  • Rabbits
  • Humans
  • Rats
  • Malaria
  • Sesquiterpenes
  • Artemisinins
  • Antimalarials
  • Drug Administration Routes
  • Developing Countries
  • Clinical Trials as Topic
  • Drug-Related Side Effects and Adverse Reactions
  • Artesunate
  • Artemether
Sprache
eng
Medium
Print
Paginierung
405 - 421
Datum der Veröffentlichung
2010
Status
Published
Datum der Datenerfassung
2010
Titel
Toxicity of the antimalarial artemisinin and its dervatives.
Sub types
  • Review
  • Journal Article
Ausgabe der Zeitschrift
40

Data source: Europe PubMed Central

Abstract
As long as no effective malaria vaccine is available, chemotherapy belongs to the most important weapons fighting malaria. One of the most promising new drug developments is the sesquiterpene artemisinin (ARS) and its derivatives, e.g., artemether, arteether, and sodium artesunate. Large clinical studies and meta-analyses did not show serious side effects, although proper monitoring of adverse effects in developing countries might not be a trivial task. There is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity. Therefore, a final and definitive statement on the safety of artemisinins still cannot be made. In contrast, animal experiments show considerable toxicity upon application of artemisinins. In the present review, the authors give a comprehensive overview on toxicity studies in cell culture and in animals (mice, rats, rabbits, dogs, monkeys) as well as on toxicity reported in human clinical trials. The authors emphasize the current knowledge on neurotoxicity, embryotoxicity, genotoxicity, hemato- and immunotoxicity, cardiotoxicity, nephrotoxicity, and allergic reactions. The lesson learned from animal and human studies is that long-term availability rather than short-term peak concentrations of artemisinins cause toxicity. Rapid elimination of artemisinins after oral intake represents a relatively safe route of administration compared to delayed drug release after intramuscular (i.m.) injection. This explains why considerable toxicities were found in the majority of animal experiments, but not in human studies. In addition, there are drug-related differences, i.e., intramuscular application of artemether or arteether, but not to artesunate, which is safe and gives good profiles after i.m. administration in severe malaria. Although there is no need to increase doses of artemisinins for uncomplicated malaria, this has to be taken into account for cerebellar involvement in severe malaria. It might also be important in determining dose limitations for treatment of other diseases such as cancer.
Autoren
  • Thomas Efferth
  • Bernd Kaina
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/20158370
DOI
10.3109/10408441003610571
eISSN
1547-6898
Ausgabe der Veröffentlichung
5
Zeitschrift
Crit Rev Toxicol
Schlüsselwörter
  • Animals
  • Antimalarials
  • Artemether
  • Artemisinins
  • Artesunate
  • Clinical Trials as Topic
  • Developing Countries
  • Dogs
  • Drug Administration Routes
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Malaria
  • Rabbits
  • Rats
  • Sesquiterpenes
Sprache
eng
Country
England
Paginierung
405 - 421
Datum der Veröffentlichung
2010
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2010
Titel
Toxicity of the antimalarial artemisinin and its dervatives.
Sub types
  • Journal Article
  • Review
Ausgabe der Zeitschrift
40

Data source: PubMed

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