Artemisinin comparative studies

The direct analysis of artemisinin from Artemisia annua L. by HPLC, GC <2006JCH(1133)254>, and HPLC-ESI-TOF MS (ESI = electrospray ionization TOE = time-of-flight) <2006JCH(1118)180> has been reviewed and a comparative study of assessment technologies for the extraction of artemisinin from the same natural product was published <2006JNP1653>. 

Comparative studies Artemisinin derivatives have been compared with quinine in cerebral malaria in African children nine randomized clinical trials were included in the analysis [9M] pjyg trials had adequate allocation concealment. Seven compared artemether with quinine ( =1220) and two compared arteether with quinine ( = 194). There were no significant differences between artemisinin derivatives and quinine in preventing mortality (RR=0.91 95% CI=0.73,1.1). The only serious adverse event was fatal black water disease in a patient who took quinine. 

Comparative studies A total of 401 adulf malaria subjecfs were enrolled in a Phase 111, randomised, open-label, mulficenfer study and received either a single dose (four tablets) of artemisinin-naphthoquine (AN) or DHP three to four tablets single daily dose for 3 days [26 ]. The patients were followed up to day 42 for physical examination and thick and thin smears microscopy. Efficacy of the drug was assessed by polymerase chain reaction (PCR). 

Deoxoartemisinin and carboxypropyldeoxoartimisinin have also been shown to have anti-tumour activity and, NMR studies on solution conformations have been reported <00BBR359>. One of the problems with artemisinin use is its poor water solubility characteristics. An attempt to rectify this, and to overcome stability problems associated with sodium artesunate in solution, has involved the introduction of amino group functionality as in 127 (eg. R = 0(CH2)3NR r2 where NR r2 = morpholine). The maleate salt of this compound has reasonable water solubility and aqueous solutions are stable at room temperature for an extended time. However activity against Plasmodium knowlesi in rhesus monkeys after oral administration was poorer compared with artesunic acid <00JMC1635>. 

Artemisinin-based regimens are often regarded as safe and effective drugs in the recent years however, clinically relevant artemisinin resistance has been reported both from laboratory and field studies. Some of these studies have shown that P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thailand. This resistance was characterized by a slow parasite clearance in vivo, without corresponding reductions on conventional in vitro susceptibility testing.Although this resistance to artemisinin is still very mild and limited, its emergence would be disastrous because of the lack of alternative treatments. 

These values were compared with independent estimates of the °roor/ro ,ro values from thermochemical cycles, where data were available to evaluate them. In the case of di-cumyl peroxide, for example, the E° obtained experimentally differs from the result of a thermodynamic calculation by only 30 mV. It is of interest to note that the uncorrected a data would have led to °roor/rovro values only slightly negative to the corrected ones (0.06-0.07 V). The good agreement in these cases was used as the basis to support the use of the convolution approach to estimate °roor/rovro for systems where the necessary values for thermochemical estimates are not available. This has been particularly useful in the study of endoperoxides and was used to estimate the standard reduction potential of the antimalarial agent, artemisinin. ... 

A large trial of the first fixed-dose combination of an artemisinin derivative likely to be licensed (artemether + benflumetol) had disappointing relapse rates compared with mefloquine monotherapy (6). In the 126 patients who took artemether + benflumetol there were no adverse effects attributed to drug treatment. However, less than 70% of patients were cured at 28 days. Benflumetol may be more effective at higher concentrations (12) but toxicity studies are lacking. 

Jiang, H.L., Chen, K.X., Wang, H.W., Tang, Y, Chen, J.Z. and Ji, R.Y. (1994). 3D QSAR Study on Ether and Ester Analogs of Artemisinin with Comparative Molecular Field Analysis. Acta Pharmacol Sin., 15,481. 

A review of antimalarial drugs indicated that artemisinin-based compounds are not recommended for use during the first trimester of pregnancy, due to lack of safety data, but the compounds may be used during the second and third trimesters (Al Kadi 2007). An animal study published after that review indicated that an increase in postimplantation losses was observed in animals given relatively high amounts (35 or 70 mg/kg) of the compound artemisinin but not in animals given amounts comparable to the standard human dose (7 mg/kg) (Boareto et al. 2008). 

Naphthoquine + artemisinin A new anti-malarial formulation containing a fixed-dose combination of naphthoquine and artemisinin in a 1 2.5 ratio has been assessed in an open study in 28 healthy volunteers who took single oral doses of 350, 700, 1400, or 2100 mg of artemisinin + naphthoquine [18/]. The combination increased the AUC and Cmax of both artemisinin and naphthoquine compared with monotherapy. Food greatly increased the AUC of artemisinin and reduced that of naphthoquine. 

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