Artemether antimalarial

Li GQ. (1989) Clinical studies on artemisinin suppository and on artesunate and artemether. In S. Jiaxiang (ed.), Antimalarial drug development in China. National Institute of Pharmaceutical Research and Development, Beijing, People s Republic of China, pp. 69-73. 

In addition to artemisinin, other synthetic trioxanes and endoperoxides (fenozan BO-7 4 and arteflene 5 " ) have enjoyed some success arteflene reached Phase II pre-clinical trials. More recently, Vennerstrom and coworkers have reported on the outstanding antimalarial properties of several 1,2,4-trioxolanes, one of which, OZ 277 (6), has entered clinical trials in man . These exciting, easily prepared drugs will be discussed in detail later in this chapter. In order to determine the parasiticidal action of this class of antimalarial, many research groups have focused their efforts on artemisinin and its semi-synthetic derivatives (artemether, arteether and artesunate Ic, Id and le), and this is the point where our discussion will begin. 

Knowledge of local resistance patterns is important to determine the treatment regimen. There is increasing chloroquine and pyrimethamine-sulfado-xine (Fansidar) resistance in Africa and in some areas at the border of Thailand there is resistance for almost all antimalarial drugs including halofantrine, mefloquine and quinine. In these areas only the artemisinin derivatives (artemether, arteether, arte-sunate, dihydroartemisinin) are effective. 

In conclusion, the vast literature and its derivatives, particularly artesunate, artemether, and arteether, point out to the need to make these derivatives in quantities that would reduce their current production cost to make these drugs accessible to the economically underprivileged societies that are often the victims of malaria. A recent promising method in which artemisinic acid, a precursor to artemisinin, has been produced in engineered yeast. Therefore, microbially produced artemisinic acid holds promise to the syntheses of antimalarial drugs at affordable prices <2006N940>. Furthermore, anticancer activities of artemisinin 1 and its derivatives have been reviewed <2005MI995>. 

Therapy. Antimalarial therapy employs the same agents, in addition to the combinations of artemether plus lumefantrine or pyrimethamine plus sulfadoxine. 

With the Chinese claims validated in 1984 by Klayman and coworkers,94 studies in the early 1980s rapidly addressed two key issues with the advancement of artemisinin as an antimalarial drug. One, how could it be made commercially and if so, what is its mode of action Although the former question was addressed,95,96 the lack in understanding its activity was reported by Gu.97 Here, evidence from prior studies indicated that, while active analogues could be prepared, including dihydroartemisinin and artemether (Figure 3.8), the endoperoxide function was key to this activity.98 In their work, Gu and co-workers postulated that the activity arose from modification of protein synthesis within the malaria parasite, Plasmodium falciparum 1 This was followed by a series of studies that indicated that the activity of artemisinin was attenuated by addition... 

SSRIs ANTIMALARIALS- ARTEMETHER/ LUMEFANTRINE This antimalarial may cause dose-related dangerous arrhythmias A substrate, mainly of CYP3A4, which may be inhibited by high doses of fluvoxamine and to a lesser degree by fluoxetine Manufacturers recommend avoidance of antidepressants... 

SNRIs ANTIMALARIALS - ARTEMETHER/ LUMEFANTRINE t artemether/lumefantrine levels with risk of toxicity, including arrhythmias Venlafaxine inhibits CYP3A4, which is partly responsible for the metabolism of artemether Avoid co-administration with venlafaxine and caution with duloxetine... 

TRYPTOPHAN ANTIMALARIALS -ARTEM ETHER/ LUMEFANTRINE T artemether/lumefantrine levels, with risk of toxicity, including arrhythmias Uncertain Avoid co-administration... 

ATOMOXETINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS — macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/dalfopristin 3. ANTICANCER AND IMMUNOMODU-LATING DRUGS - arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafax-ine 5. ANTIEMETICS - dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -artemether with lumefantrine, chloro-quine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS-pentamidine isetionate 10. ANTIPSY-CHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS - parenteral bronchodilators Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

ANTIMALARIALS - artemether with lume-fantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTI-PSYCHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS -atomoxetine... 

DRUGS TO TREAT INFECTIONS ANTIMALARIALS Artemether with lumefantrine... 

ARTEMETHER WITH LUMEFANTRINE H2 RECEPTOR BLOCKERS -CIMETIDINE t efficacy and adverse effects of antimalarials Inhibition of metabolism, some definitely via CYP3A4 Avoid co-administration... 

PROTEASE INHIBITORS ANTIMALARIALS -ARTEMETHER WITH LUMEFANTRINE t artemether levels Uncertain possibly inhibited metabolism Avoid co-administration... 

ANTIMALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 8. ANTIPROTOZOALS-pentamidine isetionate... 

---