Doses Of Dihydroartemisinin Research Articles

Respiratory Tract-Widening Effects of Dihydroartemisinin in Wistar Albino Rats

Problem statement: Artemisinin-based anti-malarials are currently widely used in Asia and Africa. Not much is known about the systemic effect of dihydroartemisinin. This study therefore examine the effect of dihydroartemisinin on the lungs of Wistar albino rats. Approach: Five dosages of Dihydroartemisinin (DHA) were administered by oral intubation for 5 days to 5 test and 4 control Wistar albino rats. Distilled water was administered to the control albino rats. The dosages of DHA tested were 1 mg kg-1 repeated after an interval of one week 2, 60 and 80 mg kg-1 A histological examination of the tissues of the lungs showed that dihydroartemisinin treatment caused a dose dependent widening of the lumen of the bronchial tree of the lungs of the test rats but not those of the control rats. The 2 mg kg-1 dose of DHA was the maximal response dose. Repetition of the same 1 mg kg-1 dihydroartemisinin dosage after an interval of one week also produced widening effects on the bronchial tree of the test rats but not on those of the control albino rats. Results: These results suggest that widening of the air tubes of the lungs and thus increasing the volume of inspired air (by the DHA-treated subject), is an important mechanism of action of dihydroartemisinin its efficacious rapid cure of malaria. Conclusion: The findings of this study suggest that dihydroartemisinin could be explore at a future drug to be use in aiding asthma patients.

Artemisinin‐Induced Dormancy inPlasmodium falciparum: Duration, Recovery Rates, and Implications in Treatment Failure

Despite the remarkable activity of artemisinin and its derivatives, monotherapy with these agents has been associated with high rates of recrudescence. The temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to artemisinin drugs provides a plausible explanation for this phenomenon. Ring-stage parasites of several Plasmodium falciparum lines were exposed to different doses of dihydroartemisinin (DHA) alone or in combination with mefloquine. For each regime, the proportion of recovering parasites was determined daily for 20 days. Parasite development was abruptly arrested after a single exposure to DHA, with some parasites being dormant for up to 20 days. Approximately 50% of dormant parasites recovered to resume growth within the first 9 days. The overall proportion of parasites recovering was dose dependent, with recovery rates ranging from 0.044% to 1.313%. Repeated treatment with DHA or with DHA in combination with mefloquine led to a delay in recovery and an approximately 10-fold reduction in total recovery. Strains with different genetic backgrounds appeared to vary in their capacity to recover. These results imply that artemisinin-induced arrest of growth occurs readily in laboratory-treated parasites and may be a key factor in P. falciparum malaria treatment failure.

Pharmacokinetics of dihydroartemisinin in Artekin tablets for single and repeated dosing in Chinese healthy volunteers

Aim. To study the pharmacokinetics of dihydroartemisinin (DHA) in Artekin (compound dihydroartemisinin) tablets in Chinese healthy volunteers. Methods. Eighteen healthy volunteers (9 males, 9 females) received Artekin tablets for oral administration. The plasma samples of DHA were analysed by liquid-liquid extraction and determined by HPLC/ESI/MS. Results. The plasma DHA concentration-time curves of single dose and repeated doses of DHA were fitted to a two-compartment open model. The mean pharmacokinetic parameters of DHA in a single dose were: t(1/2(beta))=1.245 +/- 0.495 h, C(max)=243.6 +/- 56.15 microg/l, AUC(0 --> infinity)=450 +/- 69 h x microg/l, V(d)=5.75 +/- 2.2 l/kg and Cl=3.245 +/- 0.38 l/h/kg, while in repeated doses they were: t(1/2(beta))=1.085 +/- 0.298 h, AUC(0 --> infinity)=444.35 +/- 80.43 h x ng/ml, V(d)=4.62 +/- 1.128 ml/kg, Cl=3.0125 +/- 0.875 ml/h/kg, respectively. Conclusion. The study showed that DHA in Artekin was rapidly absorbed, distributed and eliminated in the healthy subjects. The pharmacokinetic properties of DHA in Artekin were not affected by gender in a single dose. While in repeated doses accumulation of DHA did not appear after repeated doses.

Evaluation of the safety and relative bioavailability of a new dihydroartemisinin tablet formulation in healthy Thai volunteers

A new dihydroartemisinin (DHA) tablet formulation has been developed by the Thai Government Pharmaceutical Organization (GPO). In this report, its in vitro dissolution and in vivo pharmacokinetics as well as its safety in healthy volunteers were evaluated, using the DHA tablet made by Dafra Pharma NV as a reference. A two-period crossover clinical study design was utilised. Twenty-four volunteers were randomly allocated to two sequences (12 volunteers in each) to receive a 200mg single oral dose of either the GPO or Dafra formulation with a wash-out period of 5-7 days. In vitro, the GPO formulation dissolved more readily. In vivo, the GPO formulation had a higher maximum plasma concentration and approximately 149% (90% CI 125-179%) greater bioavailability. Both formulations were well tolerated. Interestingly, significant decreases in haemoglobin and haematocrit values (P<0.001) were noted following administration of one dose of DHA (decrease of 0.73 g/dl haemoglobin and 2.0% haematocrit compared with baseline) or two doses of DHA (decrease of 0.95 g/dl haemoglobin and 3.3% haematocrit compared with baseline). The second dose was associated with additional toxicity compared with one dose with regard to haematocrit (P<0.001) but not haemoglobin. This finding warrants further investigation, since the drug will be used for the treatment of malaria in which anaemia is a consequence.