Qinghaosu (ARTEMISININ)

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* Health and Healing *

Tuesday, April 23, 2002 7:49 AM

Qinghaosu (ARTEMISININ)

 

 

- http://homepages.uel.ac.uk/4474p/qingh.htm -

 

Qinghaosu (ARTEMISININ)

Artemisinin was originally developed in 1972 in China (Chines Institute of

material medicine) from the plant Artemisia annua L (sweet wormwood), a

sesquiterpene lactone (emperical formula C15 H22 O5. Artemisinin is the active

ingredient in qinghao, a Chinese herbal tea that have been used for 150 years to

treat malaria and haemorrhoids. It grows in the wild in China and now has been

found to grow in other parts of the world too, though the species may vary a

bit. Locally, it is prepared as an infusion of the dried leaves. (Click here to

see Sweetwormwood, the herbs)

 

Derivatives of Artemisinin are; artemether, artesunate, arteether and

artelinate. Artemisinin and these compounds are quickly converted to their

active plasma metabolite, dihydroartemisinin, which is the chemical with the

anti-malarial activity.

 

Artemisinin, artemether and arteether are water insoluble, artesunate and

artelinate are water-soluble

(Click here to see chemical structures of Artemisinin and derivatives).

 

 

 

 

 

 

 

MECHANISM OF ACTION

 

 

 

 

 

 

Artemisinin is a rapid parasiticidal of the asexual stages; it is

anti-gametocyte and blocks sporogony (heppner and Ballou 1998). It produces

ultra-structural changes to the growing trophozoite parasite. A whorl is

produced in the food vacuole and the parasite’s mitochondria proliferated. This

reduces parasite's survival (Hien and White 1993). Endoperoxide bridge is

essential for its anti-malarial activity. The compound is activated by the

intra-parasitic haem to irreversibly decompose, generating free radicals that

alkylate and oxidises proteins and lipids. The membrane of the parasite is

damaged by lipid peroxidation and channel proteinsEinactivation. (Ridley &

Hudson 1998). Parasites clearance times are shorter than with chloroquine and

also symtomatic response.

 

 

 

 

 

 

PARMACOKINETICS

 

 

 

 

 

 

Clinical evaluation of therapeutic regimens is required to validate clinical

efficacy of this promising drug (Oduola et al 1998). Artemisinin has a quick

onset of action thereby, stoping the parasites from developing and cytoadherence

is not reached. Drug disposition of Artemisinin after oral administration has

been determined, using a one-compartment model with separate pharmacokinetic

estimates for children and adults. The population estimates for Artemisinin

clearance and distribution volume, respectively, were 432 Lh-1 and 1600 L for

adults and 14.4 Lh-1 kg-1 and 37.9 Lkg-1 for children, with an inter-subject

variability (collectively for both age groups) of 45% and 104%, respectively.

The oral bioavailability was estimated to decrease from Day 1 to Day 5 by a

factor of 6.9, a value found to be similar for children and adults (Sidhu et al.

1998). Half-lives of Artemisinin is 4hrs, artesunate, 45 min and artemether,

4-11 hrs (Batty et al 1998). Findings like this have advocated the dosing of

Artemisinin to children according to bodyweight and to adults according to a

standard dose.

 

 

 

 

CLINICAL USES

 

 

 

 

 

 

 

Warrell, D. A. (1977) predicted that Artemisinin and derivatives would become

the treatment of choice in the coming decade. Artemisinin, artemether,

artesunate, arteether are now widely used in South East Asia, some parts of

Africa, while artelinate is a research agent in the Walter Reed Army Institute

of Research. Washington D. C. Artemisinin derivatives have become the treatment

of choice in the coastal parts of Malaya, Sarawak, Singapore and Asia Pacific

region. Clinical efficacy, in terms of parasites clearance and fever subsidence

times, was comparable between children and adults. Within 48 hr, 70% of the

cases do become afebrile and the peripheral smears usually negative in 100% of

the cases. The drugs are well tolerated.

 

 

 

 

 

TOXICITY

 

 

 

 

 

 

 

Well-documented clinical uses of Artemisinin and derivatives have shown few

insignificant side effects, but findings in rats' studies are causing

controversy. Intra-muscular arteether at 25-mg/ Kg/ day resulted in rats'

brainstem pathology with damage to the auditory nuclei. Parenteral artemether in

the treatment of cerebral malaria in Gambien children shows a prolonged recovery

from coma and post-treatment convulsions than the same treatment with quinine.

Also in Vietnamese adults, a prolonged recovery was noted, but no increased in

mortality or neurological behaviour afterwards (Heppner and Ballou 1998). Others

are transient heart block, transient decrease in blood neutrophills and brief

episodes of fever.

 

 

 

 

 

COMBINATION THERAPY

 

 

 

 

 

 

Short course artemether as monotherapy have been shown to be limited by

secondary malaria episodes. Therefore long term, combinations are now being

tried. In rodent studies, Artemisinin potentiates the effects of mefloquine,

primaquine and tetracycline. (Hien and White. 1993). Thailand’s multi-drug

resistant P. falciparum malaria (uncomplicated acute) is now treatable with

artemether-mefloquine as a short course treatment, which has good patients

compliance, clinical effectiveness, efficacy, tolerability. Low dose intravenous

artesunate followed by mefloquine was found to be well tolerated and rapidly

effective in treating severe falciparum malaria contracted in Indonesia and

India. There was no relapse of clinical disease in all four cases after 28 days.

 

 

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