Pharmacokinetic (PK) and Pharmacodynamic Profiles of Artemisinin Derivatives Influence Drug Neurotoxicity in Animals

Li, Qigui; Hickman, Mark

doi:10.5772/33352

Cited by 2 publications

(2 citation statements)

References 64 publications

(113 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reports of adverse effects in humans exist. In as much as it can be considered academic pomposity to disregard clinical reports that seem to establish causal relationship between certain neurological manifestations in human (Panossian et al, 2005;Franco-Paredes et al, 2005;Elias et al, 1999) and artemisinin compounds it should be noted that, these reports are in the minority and some Writers (Li and Hickman, 2012) question the basis of the Authors' conclusions.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…Still in support of lipophilicity being essential for neurotoxicity, Sanjana et al (2012) demonstrated that, in consonance with its lipophobicity profile artesunate effectively suppressed convulsive episodes in the maximal electro-shock seizure model of epilepsy in albino mice. In another angle to the neurotoxicity potentials of artemisinin compounds, Li and Hickman (2012) examined the role of:…”

Section: Pharmacokineticsmentioning

confidence: 99%

See 1 more Smart Citation

Artemisinin: An Evolving Antimalarial-Part One

Edikpo¹,

Adikwu²

2013

BJPT

View full text Add to dashboard Cite

This review was conceived with the aim of presenting a compact, yet engaging account of the evolution of artemisinin from its humble and ancient origins as an herbal remedy to a modern chemotherapeutic agent, highlighting its unique pharmacological and toxicological profile and the central position it occupies at present in the battle against malaria. Artemisinin is a sesquiterpene lactone end operoxide with a long and enchanting history. The Chinese had been using concoctions of Artemisia for the treatment of various febrile ailments for close to two millennia. The impetus for its extraction in 1972 from Artemisia annua came from the battlefields of the Vietnamese war of 1965 to 1973 and the political milieu of the Cultural Revolution that encouraged an inward-looking disposition. Owing to solubility problems with the parent compound, artemisinin other semi-synthetic derivatives are now available and include artesunate, artemether, dihydroartemisinin and arteether. Parasiticidal action resides in the endoperoxide moiety which is also primarily responsible for the toxicity of the artemisinin compounds. As a class, they are the most rapidly acting antimalarial chemotherapeutic agents ever in use, reducing initial parasite burden by a factor of 10 4 per cycle of schizogony. Despite this, high rate of recrudescence occur with monotherapies which necessitates their use in combination with longer acting agents-ACTs. The basis of this high recrudescence is not unrelated to short plasma half-lives, dormancy phenomenon and autoinduction of the metabolizing enzymes. Though safe in humans at recommended dosages, animal studies have continually revealed disturbing side effects most notably, neurotoxicity and, reproductive toxicity manifesting in the twin phenomenon of embryolethality and fetal dysmorphogenesis. In the light of the cautionary tale of thalidomide tragedy, it may not be wise to totally ignore these findings in experimental animals.

show abstract