Skip to main content
SpringerLink
Log in

Clinical Pharmacology and Therapeutic Potential of Artemisinin and its Derivatives in the Treatment of Malaria

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Artemisinin and its derivatives are renowned for their potent antimalarial activity. They have found their way into clinical use in many areas where malaria is endemic. The in vitro concentration at which artemisinin can inhibit 50% of the growth of Plasmodium falciparum ranges from 3 to 30 μg/L. The fat-soluble derivatives artemether and arteether are approximately twice as active. The water-soluble dihydro-artemisinin and artesunate are 4 to 5 times more active in vitro. Artemisinin is available only for oral and rectal administration. Absorption is incomplete and elimination is fast, with an elimination half-life of 2 to 5 hours. Plasma concentrations after a single 500mg oral dose most often exceed 200 μg/L. Artesunate and artemether can be considered as prodrugs. Biotransformation into the active metabolite dihydro-artemisinin occurs rapidly — almost immediately for artesunate. The reported elimination half-life of artesunate is less than 1 hour, and for artemether the figure is 3 to 11 hours. The pharmacokinetics of dihydro-artemisinin are not yet completely clear. Elimination is probably also rapid, with an elimination half-life of a few hours. Arteether, dissolved in oil for intramuscular administration, has a much longer elimination half-life of over 20 hours.

The clinical efficacy of this group of drugs is characterised by an almost immediate onset and rapid reduction of parasitaemia, with complete clearance in most cases within 48 hours. Efficacy is high even in areas with multidrug-resistant parasite strains. To prevent recrudescence with monotherapy of these compounds, treatment needs to be extended beyond the disappearance of parasites. After 5 days of therapy the rate of recrudescence is approximately 10%. Alternatively, combination with other drugs can be used. Combination with mefloquine is recommended for areas with multidrug-resistant P. falciparum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Klayman DL. Qinghaosu (artemisinin): an antimalarial drug from China. Science 1985; 228: 1049–1055

    Article  CAS  PubMed  Google Scholar 

  2. Luo X-D, Shen C-C. The chemistry, pharmacology, and clinical applications of qinghaosu (artemisinin) and its derivatives. Med Res Rev 1987; 7: 29–52

    Article  CAS  PubMed  Google Scholar 

  3. Webster HK, Lehnert EK. Chemistry of artemisinin: an overview. Trans R Soc Trop Med Hyg 1994; 88: S1/27–S1/29

    Article  Google Scholar 

  4. Li G-Q, Guo X-B, Fu L-C, et al. Clinical trials and its derivatives in the treatment of malaria in China. Trans R Soc Trop Med Hyg 1994; 88: S1/5–S1/8

    Article  Google Scholar 

  5. Hien TT. An overview of the clinical use of artemisinin and its derivatives in the treatment of falciparum malaria in Vietnam. Trans R Soc Trop Med Hyg 1994; 88: S1/7–S1/8

    Article  Google Scholar 

  6. Looareesuwan S. Overview of clinical studies on artemisnin derivatives in Thailand. Trans R Soc Trop Med Hyg 1994; 88: S1/9–S1/11

    Article  Google Scholar 

  7. Sy ND, Hoan DB, Dung NP, et al. Treatment of malaria in Vietnam with oral artemisinin. Am J Trop Med Hyg 1993; 48: 398–402

    Article  Google Scholar 

  8. Brossi A, Venugopalan B, Dominguez Gerpe L, et al. Arteether, a new antimalarial drug: synthesis and antimalarial properties. J Med Chem 1988; 31: 645–50

    Article  CAS  PubMed  Google Scholar 

  9. Day M. Malaria falls to herbal remedy. New Sci 1996 Jul 13; 151: 4

    Google Scholar 

  10. Mishra SK, Asthana OP, Mohanty S et al. Effectiveness of α, β-arteether in acute falciparum malaria. Trans R Soc Trop Med Hyg 1995; 89: 299–301

    Article  CAS  PubMed  Google Scholar 

  11. Meshnick SR, Taylor TE, Kamchongwongpaisan S. Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiol Rev 1996; 60: 301–15

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Meshnick SR, Yang YZ, Lima V, et al. Iron-dependent free radical generation and the antimalarial artemisinin (qinghaosu). Antimicrob Agents Chemother 1993; 37: 1108–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gu HM, Warhurst DC, Peters W. Uptake of [3H] dihydroartemisinin by erythrocytes infected with Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 1984; 78: 265–70

    Article  CAS  PubMed  Google Scholar 

  14. Maeno Y, Brown AE, Smith CD, et al. A nonhuman primate model for human cerebral malaria: effects of artesunate (qinghaosu derivative) on rhesus monkeys experimentally infected with Plasmodium coatneyi. Am J Trop Med Hyg 1993; 49: 726–34

    Article  CAS  PubMed  Google Scholar 

  15. Kaiwa S, Kano S, Suzuki M. Morphologic effects of artemether on Plasmodium falciparum in Aotus trivirgatus. Am J Trop Med Hyg 1993; 49: 812–8

    Article  Google Scholar 

  16. ter Kuile FO, Holloway NJ, Pasvol G, et al. Plasmodium falciparum: in vitro studies of the pharmacodynamic properties used for the treatment of severe malaria. Exp Parasitol 1993; 49: 106–12

    Google Scholar 

  17. Basco LK, Le Bras J. In vitro activity of artemisinin derivatives against African isolates and clones of Plasmodium falciparum. Am J Trop Med Hyg 1993; 49: 301–7

    Article  CAS  PubMed  Google Scholar 

  18. Hassan Alin M, Björkman A, Landberg-Lindgren A, et al. The effect of artemisinin, its derivatives and mefloquine against chloroquine-resistant strains of Plasmodium falciparum in vitro. Trans R Soc Trop Med 1992; 86: 365–7

    Article  CAS  Google Scholar 

  19. Hassan Alin M, Björkman A, Ashton M. In vitro activity of artemisinin, its derivatives, and pyronaridine against different strains of Plasmodium falciparum. Trans R Soc Trop Med Hyg 1990; 84: 635–7

    Article  Google Scholar 

  20. Doury JC, Ringwald P, Guelain J, et al. Susceptibility of African isolates of Plasmodium falciparum to artemisinin (qinghaosu). Trop Med Parasitol 1992; 43: 197–8

    CAS  PubMed  Google Scholar 

  21. Lin AJ, Lee M, Klayman DL. Antimalarial activity of new water-soluble dihydroartemisinin derivatives: 2. Stereospecificity of the ether side chain. J Med Chem 1989; 32: 1249–52

    Article  CAS  PubMed  Google Scholar 

  22. Lin AJ, Klayman DL, Milhous WK. Antimalarial activity of new water-soluble dihydroartemisinin derivatives: 1. J Med Chem 1987; 30: 2147–50

    Article  CAS  PubMed  Google Scholar 

  23. Lin AJ, Li L, Andersen SL, et al. Antimalarial activity of new dihydroartemisinin derivatives: 5. Sugar analogues. J Med Chem 1992; 35: 1639–42

    Article  CAS  PubMed  Google Scholar 

  24. Thaithong S, Beale GH. Susceptibility of Thai isolates of Plasmodium falciparum to artemisinine (qinghaosu) and artemether. Bull World Health Organ 1985; 63: 617–9

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Li ZL, Gu HM, Warhurst DC, et al. Effects of qinghaosu and related compounds on incorporations of [G-3H] hypoxanthine by Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 1983; 77: 522–3

    Article  CAS  PubMed  Google Scholar 

  26. Shmuklarsky MJ, Klayman DL, Milhous WK, et al. Comparison of /gb-artemether and /gb-arteether against malaria parasites in vitro and in vivo. Am J Trop Med Hyg 1993; 48: 377–84

    Article  CAS  PubMed  Google Scholar 

  27. Ye Z-G, Van Dyke K, Wimmer M. Effect of artemisinin (qinghaosu) and chloroquine on drug-sensitive and drug-resistant strains of Plasmodium falciparum malaria: use of [2, 8-3H]adenosine as an alternative to [G-3H]hypoxanthine in the assessment of in vitro antimalarial activity. Exp Parasitol 1987; 64: 418–23

    Article  CAS  PubMed  Google Scholar 

  28. Ekong R, Warhurst DC. Synergism between arteether and mefloquine in a multidrug-resistant strain of Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 1990; 84: 757–8

    Article  CAS  PubMed  Google Scholar 

  29. Hassan Alin M, Bjorkman A. Concentration and time dependency of artemisinin efficacy against Plasmodium falciparum in vitro. Am J Trop Med Hyg 1994; 50: 771–6

    Article  Google Scholar 

  30. Chawira AN, Warhurst DC, Peters W. Drug combination studies with Qinghaosu (Artemisinin) against sensitive and resistant strains of rodent malaria. Trans R Soc Trop Med Hyg 1986; 80: 334–5

    Article  Google Scholar 

  31. Chawira AN, Warhurst DC, Peters W. Artemisinin (Qinghaosu) combinations against chloroquine- sensitive and resistant Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 1986; 80: 335

    Article  Google Scholar 

  32. Inselburg J. Induction and isolation of artemisinine-resistant mutants of Plasmodium falciparum. Am J Trop Med Hyg 1985; 34: 417–8

    Article  CAS  PubMed  Google Scholar 

  33. Gay F, Ciceron L, Litaudon M, et al. In-vitro resistance of Plasmodium falciparum to qinghaosu derivatives in West Africa. Lancet 1994; 343: 850–1

    Article  CAS  PubMed  Google Scholar 

  34. Dutta GP, Mohan A, Tripathi R. Study of the gametocytocidal action of qinghaosu (artemisinin) by electron microscopy. J Parasitol 1990; 76: 849–52

    Article  CAS  PubMed  Google Scholar 

  35. Kumar N, Zheng H. Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. Parasitol Res 1990; 76: 214–8

    Article  CAS  PubMed  Google Scholar 

  36. Price RN, Nosten F, Luxemburger C, et al. Effects of artemisinin derivatives on malaria transmissibility. Lancet 1996; 347; 1654–8

    Article  CAS  PubMed  Google Scholar 

  37. Thomas CG, Ward SA, Edwards G. Selective determination, in plasma, of artemether and its major metabolite, dihydroartemisinin, by high-performance liquid chromatography with ultraviolet detection. J Chromatogr 1992; 583: 131–6

    Article  CAS  PubMed  Google Scholar 

  38. Titulaer HAC, Zuidema J, Kager PA, et al. The pharmacokinetics of artemisinin after oral, intramuscular and rectal administration to volunteers. J Pharm Pharmacol 1990; 42: 810–3

    Article  CAS  PubMed  Google Scholar 

  39. Zhou ZM, Zeng MYZLL, Nie SQ, et al. Pharmacokinetic studies of artemisinin (qinghaosu) and its derivatives by high-performance liquid chromatographic methods. Antimalarial Drug Development in China: 1989 Apr 24–26; Beijing

  40. Zhao S. High-performance liquid chromatographic determination of artemisinine (qinghaosu) in human plasma and saliva. Analyst 1987; 12: 661–4

    Article  Google Scholar 

  41. Hassan Alin M, Ashton M, Kihamia CM, et al. Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients. Trans R Soc Trop Med Hyg 1996; 90: 61–5

    Article  CAS  PubMed  Google Scholar 

  42. Acton N, Klayman DL, Rollman IJ. Reductive electrochemical HPLC assay for artemisinin (qinghaosu). Planta Medica 1985; 445-6

  43. Zhou ZM. Analysis of artesunic acid and dihydroqinghaosu in blood by high-performance liquid chromatography with reductive electrochemical detection. J Chromatogr 1987; 414: 77–90

    Article  CAS  PubMed  Google Scholar 

  44. Melendez V, Peggins JO, Brewer TG, et al. Determination of the antimalarial arteether and its deethylated metabolite dihydroartemisinin in plasma by high-performance liquid chromatography with reductive electrochemical detection. J Pharm Sci 1991; 80: 132–8

    Article  CAS  PubMed  Google Scholar 

  45. Duc DD, de Vries PJ, Khanh NX, et al. The pharmacokinetics of a single dose of artemisinin in healthy Vietnamese subjects. Am J Trop Med Hyg 1994; 51: 785–90

    Article  CAS  PubMed  Google Scholar 

  46. Mount DL, Todd GD, Navaratnam V. Packed-column supercritical fluid chromatography of artemisinin (qinghaosu) with electron-capture detection. J Chromatogr 1995; 666: 183–7

    Article  CAS  Google Scholar 

  47. Green MD, Mount DL, Todd GD, et al. Chemiluminiscent detection of artemisinin. Novel endoperoxide analysis using luminol without hydrogen peroxide. J Chromatogr 1995; 695: 237–42

    Article  CAS  Google Scholar 

  48. Li X, Rieckmann K. A bioassay for derivatives of qinghaosu (artemisinin). Trop Med Parasitol 1992; 43: 195–6

    CAS  PubMed  Google Scholar 

  49. Teja-Isavadharm P, White NJ, Brewer TG, et al. Pharmacokinetic (PK) and pharmacodynamic (PD) of a single dose of artemether (AM) by three routes of administration in healthy Caucasian volunteers [abstract]. Am J Trop Med Hyg 1995; 53 Suppl.: 203

    Google Scholar 

  50. Batty KT, Ilett KF, Davis TME. Chemical stability of artesunate injection and proposal for its administration by intravenous infusion. J Pharm Pharmacol 1996; 48: 22–6

    Article  CAS  PubMed  Google Scholar 

  51. Niu X, Ho L, Ren Z, et al. Metabolic fate of qinghaosu in rats; a new TLC densitometric method for its determination in biological material. Eur J Drug Metab Pharmacokinet 1985; 10: 55–9

    Article  CAS  PubMed  Google Scholar 

  52. Leskovac V, Theoharides AD. Hepatic metabolism of artemisinin drugs: I. Drug metabolism in rat liver microsomes. Comp Biochem Physiol 1991; 99C: 383–90

    CAS  Google Scholar 

  53. Leskovac V, Theoharides AD. Hepatic metabolism of artemisinin drugs: II. Metabolism of arteether in rat liver cytosol. Comp Biochem Physiol 1991; 99C: 391–6

    CAS  Google Scholar 

  54. Lee I-S, Hufford CD. Metabolism of antimalarial sesquiterpene lactones. Pharmac Ther 1990; 48: 345–55

    Article  CAS  Google Scholar 

  55. Augustijns P, D’Hulst A, van Daele J, et al. Transport of artemisinin and sodium artesunate in caco-2 intestinal epithelial cells. J Pharm Sci 1996; 85: 577–9

    Article  CAS  PubMed  Google Scholar 

  56. Zhao KC, Song ZY. Pharmacokinetics of dihydroqinghaosu in human volunteers and comparison with qinghaosu. Acta Pharmaceutical Sinica 1993; 28: 342–6

    CAS  Google Scholar 

  57. Na Bangchang K, Karbwang J, Thomas CG, et al. Pharmacokinetics of artemether after oral administration to healthy Thai males and patients with acute, uncomplicated falciparum malaria. Br J Clin Pharmacol 1994; 37: 249–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Benakis A, Paris M, Plessas C, et al. Pharmacokinetics of sodium artesunate after im and iv administration [abstract]. Am J Trop Med Hyg 1993; 293 Suppl.: 293

    Google Scholar 

  59. Batty KT, Davis TME, Thu LTA, et al. Selective high-performance liquid chromatographic determination of artesunate and α- and /gb-dihydroartemisinin in patients with falciparum malaria. J Chromatogr B Biomed Appl 1996; 677; 345–50

    Article  PubMed  Google Scholar 

  60. Zhou ZM, Huang YX, Xie GH, et al. HPLC with polarographic detection of artemisinin and its derivatives and application of the method to the pharmacokinetic study of artemether. J. Liq Chromatogr 1988; 11: 1117–37

    Article  CAS  Google Scholar 

  61. Kager PA, Schultz MJ, Zijlstra EE, et al. Arteether administration in humans: preliminary studies of pharmacokinetics, safety and tolerance. Trans R Soc Trop Med Hyg 1994; 88: S1/31–S1/32

    Article  Google Scholar 

  62. Murphy S, Watkins WM, Bray PG, et al. Parasite viability during treatment of severe falciparum malaria: differential effects of artemether and quinine. Am J Trop Med Hyg 1995; 53: 303–5

    Article  CAS  PubMed  Google Scholar 

  63. Watkins W, Woodrow C, Marsh K. Falciparum malaria: differential effects of antimalarial drugs on ex vivo parasite viability during the critical phase of therapy. Am J Trop Med Hyg 1993; 49: 106–12

    Article  CAS  PubMed  Google Scholar 

  64. White NJ. Clinical pharmacokinetics and pharmacodynamics of artemisinin and derivatives. Trans R Soc Trop Med Hyg 1984; 88 Suppl.: S1/41–S1/43

    Google Scholar 

  65. Li G-Q. Clinical trials on qinghaosu and its derivatives. Volume 1. Guangzhou College of Traditional Chinese Medicine, Sanya Tropical Medicine Institute, 1990

  66. China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials. Clinical studies on the treatment of malaria with qinghaosu and its derivatives. J Trad Chin Med 1982; 2: 45–50

    Google Scholar 

  67. Li G, Arnold K, Guo X, et al. Randomised comparative study of mefloquine, qinghaosu, and pyrimethamine-sulfadoxine in patients with falciparum malaria. Lancet 1984; II: 1360–1

    Article  Google Scholar 

  68. Jiang J-B, Li G-Q, Guo X-B, et al. Antimalarial activity of mefloquine and qinghaosu. Lancet 1982; II: 285–8

    Article  Google Scholar 

  69. Sy ND, Hoan DB, Dung NP, et al. Treatment of malaria in Vietnam with oral artemisinin. Am J Trop Med Hyg 1993; 48: 398–402

    Article  Google Scholar 

  70. Arnold K, Hien TT, Chinh NT, et al. A randomized comparative study of artemisinine (qinghaosu) suppositories and oral quinine in acute falciparum malaria. Trans R Soc Trop Med Hyg 1990; 84: 499–502

    Article  CAS  PubMed  Google Scholar 

  71. Bich NN, de Vries PJ, Thien HV, et al. Efficacy and tolerance of artemisinin in short combination regimens for the treatment of uncomplicated falciparum malaria. Am J Trop Med Hyg 1996; 55: 438–43

    Article  CAS  PubMed  Google Scholar 

  72. Hien TT, Tarn DTH, Cuc NTK, et al. Comparative effectiveness of artemisinin suppositories and oral quinine in children with acute falciparum malaria. Trans R Soc Trop Med Hyg 1991; 85: 210–1

    Article  CAS  PubMed  Google Scholar 

  73. Hien TT, Arnold K, Vinh H, et al. Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria. Trans R Soc Trop Med Hyg 1992; 86: 582–3

    Article  CAS  PubMed  Google Scholar 

  74. Hien TT, Phu NH, Mai NTH, et al. An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria. Trans R Soc Trop Med Hyg 1992; 86: 584–5

    Article  CAS  PubMed  Google Scholar 

  75. Price RN, Nosten F, Luxemburger C, et al. Artesunate versus artemether in combination with mefloquine for the treatment of multidrug-resistant falciparum malaria. Trans R Soc Trop Med Hyg 1995; 89: 523–7

    Article  CAS  PubMed  Google Scholar 

  76. Bunnag D, Viravan C, Looareesuwan S, et al. Double blind randomised clinical trial of oral artesunate at once or twice daily dose in falciparum malaria. Southeast Asian J Trop Med Pub Health 1991; 22: 11–5

    Google Scholar 

  77. Bunnag D, Viravan C, Looareesuwan S, et al. Clinical trial of artesunate and artemether on multidrug resistant falciparum malaria in Thailand. A preliminary report. Southeast Asian J Trop Med Pub Health 1991; 22: 380–5

    CAS  Google Scholar 

  78. Karbwang J, Na-Bangchang K, Thanavibul A, et al. Comparative trial of artesunate and the combination of artesunatemefloquine in multidrug-resistant falciparum malaria. Clin Drug Invest 1996; 11: 84–9

    Article  CAS  Google Scholar 

  79. Bunnag D, Viravan C, Looareesuwan S, et al. Double blind randomised clinical trial of two different regimens of oral artesunate in falciparum malaria. Southeast Asian J Trop Med Pub Health 1991; 22: 534–8

    CAS  Google Scholar 

  80. Looareesuwan S, Viravan C, Vanijanonta S, et al. Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria. Lancet 1992; 339: 821–4

    Article  CAS  PubMed  Google Scholar 

  81. Hassan Alin M, Kihamia CM, Bjorkman A, et al. Efficay of oral and intravenous artesunate in male Tanzanian adults with Plasmodium falciparum malaria and in vitro susceptibility to artemisinin, chloroquine and mefloquine. Am J Trop Med Hyg 1995; 53: 639–45

    Article  Google Scholar 

  82. Looareesuwan S, Kyle DE, Viravan C, et al. Treatment of patients with recrudescent falciparum malaria with a sequential combination of artesunate and mefloquine. Am J Trop Med Hyg 1992; 47: 794–9

    Article  CAS  PubMed  Google Scholar 

  83. Looareesuwan S, Viravan C, Vanijanonta S, et al. Randomized trial of mefloquine-doxycycline, and artesunate-doxycycline for treatment of acute uncomplicated falciparum malaria. Am J Trop Med Hyg 1994; 784-9

  84. Looareesuwan S, Wilairatana P, Vanijanonta S, et al. Efficacy and tolerability of a sequential, artesunate suppository plus mefloquine, treatment of severe falciparum malaria. Ann Trop Med Parasitol 1995; 89: 469–75

    Article  CAS  PubMed  Google Scholar 

  85. Nosten F, Luxemburger C, ter Kuile FO, et al. Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. J Inf Dis 1994; 170: 971–7

    Article  CAS  Google Scholar 

  86. Luxemburger C, ter Kuile FO, Nosten F, et al. Single day mefloquine-artesunate combination in the treatment of multidrug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1994; 88: 213–7

    Article  CAS  PubMed  Google Scholar 

  87. Luxemburger C, Nosten F, Shotar, et al. Oral artesunate in the treatment of uncomplicated hyperparasitemic falciparum malaria. Am J Trop Med Hyg 1995; 522-5

  88. Bunnag D, Kanda T, Karbwang J, et al. Artemether or artesunate followed by mefloquine as a possible treatment for multidrug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1996; 90: 415–7

    Article  CAS  PubMed  Google Scholar 

  89. Karbwang J, Na-Bangchang K, Thanavibul A, et al. Comparison of oral artemether and mefloquine in acute uncomplicated falciparum malaria. Lancet 1992; 340: 1245–8

    Article  CAS  PubMed  Google Scholar 

  90. Karbwang J, Na-Bangchang K, Wattanakoon Y, et al. Artemether 5 versus 7 day regimen for severe falciparum malaria. Southeast Asian J Trop Med Pub Health 1994; 25: 702–6

    CAS  Google Scholar 

  91. Looareesuwan S, Wilairatana P, Vanijanonta S, et al. Treatment of acute, uncomplicated falciparum malaria with oral dihydroartemisinin. Ann Trop Med Parasitol 1996; 90: 21–8

    Article  CAS  PubMed  Google Scholar 

  92. Karbwang J, Na-Bangchang, Thanavibul A, et al. A comparative clinical trial of two different regimens of artemether plus mefloquine in multidrug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1995; 89: 296–8

    Article  CAS  PubMed  Google Scholar 

  93. Bunnag D, Kanda T, Karbwang J, et al. Artemether-mefloquine combination in multidrug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1995; 89: 213–5

    Article  CAS  PubMed  Google Scholar 

  94. Myint PT, Shwe T. A controlled clinical trial of artemether (qinghaosu derivative) versus quinine in complicated and severe malaria. Trans R Soc Trop Med Hyg 1987; 81: 559–61

    Article  Google Scholar 

  95. Win K, Than M, Thwe Y. Comparison of combinations of parenteral artemisinin derivatives plus oral mefloquine with intravenous quinine plus oral tetracycline for treating cerebral malaria. Bull World Health Organ 1992; 70: 777–82

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Shwe T, Myint PT, Htut Y, et al. The effect of mefloquineartemether compared with quinine on patients with complicated falciparum malaria. Trans R Soc Trop Med Hyg 1988; 82: 665–6

    Article  Google Scholar 

  97. White NJ, Waller D, Crawley J, et al. Comparison of artemether and chloroquine for severe malaria in Gambian children. Lancet 1992; 339: 317–21

    Article  CAS  PubMed  Google Scholar 

  98. Walker O, Salako LA, Omokhodion SI, et al. An open randomized comparative study of intramuscular artemether and intravenous quinine in cerebral malaria in children. Trans R Soc Trop Med Hyg 1993; 87: 564–6

    Article  CAS  PubMed  Google Scholar 

  99. Taylor TE, Wills BA, Kazembe P, et al. Rapid coma resolution with artemether in Malawian children with cerebral malaria. Lancet 1993; 341: 661–2

    Article  CAS  PubMed  Google Scholar 

  100. Salako LA, Walker O, Sowunmi A, et al. Artemether in moderately severe and cerebral malaria in Nigerian children. Trans R Soc Trop Med Hyg 1994; 88 Suppl.: S1/13–S1/15

    Article  Google Scholar 

  101. Karbwang J, Tin T, Rimchala W, et al. Comparison of artemether and quinine in the treatment of severe falciparum malaria in south-east Thailand. Trans R Soc Trop Med Hyg 1995; 89: 668–71

    Article  CAS  PubMed  Google Scholar 

  102. van Hensbroek MB, Onyiorah E, Jaffar S, et al. A trial of artemether or quinine in children with cerebral malaria. N Engl J Med 1996; 335: 69–75

    Article  PubMed  Google Scholar 

  103. Murphy S, English M, Waruiru C, et al. An open randomized trial of artemether versus quinine in the treatment of cerebral malaria in African children. Trans R Soc Trop Med Hyg 1996; 90: 298–301

    Article  CAS  PubMed  Google Scholar 

  104. Sowunmi A, Oduola AMJ. Efficacy of artemether in severe falciparum malaria in African children. Act Trop 1996; 61: 57–63

    Article  CAS  Google Scholar 

  105. Hien TT, Day NPJ, Phu NH, et al. A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med 1996; 335: 76–83

    Article  CAS  Google Scholar 

  106. Looareesuwan S, Wilairatana P, Vanijanonta S, et al. Efficacy and tolerability of a sequential, artesunate suppository plus mefloquine, treatment of severe falciparum malaria. Ann Trop Med Parasitol 1995; 89: 469–75

    Article  CAS  PubMed  Google Scholar 

  107. Peto TEA, Newbold CI, Pasvol G. Qinghaosu, mefloquine, and pyrimethamine-sulfadoxine in falciparum malaria. Lancet 1985; I: 216

    Article  Google Scholar 

  108. China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials and China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials and China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials and China Cooperative Research Group on Qinghaosu and Its Derivatives as Antimalarials. Studies on the toxicity of qinghaosu and its derivatives. J Trad Chinese Medicine 1982; 2: 31–8

    Google Scholar 

  109. Gu H-M, Warhusrt DC, Peters W. Hemolysis induced by artemisinin and its derivatives in vitro. Acta Pharamacologica Sinica 1986; 7: 269–72

    CAS  Google Scholar 

  110. Brewer TG, Peggins JO, Grate SJ, et al. Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg 1994; 88 Suppl.: S1/33–S1/36

    Article  Google Scholar 

  111. Fishwick J, McLean WG, Edwards G, et al. The toxicity of artemisinin and related compounds of neuronal and glial cells in culture. Chem Biol Interact 1995; 96: 263–71

    Article  CAS  PubMed  Google Scholar 

  112. Brewer TG, Petras JM, Peggins JO, et al. Differential neurotoxicity of artemisinin analogs in an in vivo model [abstract]. Am J Trop Med Hyg 1993; 49 Suppl.: 292

    Google Scholar 

  113. Wang T. Follow-up observation on the therapeutic effects and remote reactions of artemisinin (qinghaosu) and aremether in treating malaria in pregnant women. J Trad Chin Med 1989; 9: 28–30

    CAS  Google Scholar 

  114. Fu L-C, Guo X-B, Jiang H-X, et al. Follow up observations on pregnant women with malaria treated with qinghaosu and its derivatives [abstract]. In: Clinical trials on qinghaosu and its derivatives. Volume 1. Guangzhou College of Traditional Chinese Medicine, Sanya Tropical Medicine Institute: 1990, 86

  115. White NJ. Summary of discussion and conclusions. Trans R Soc Trop Med Hyg 1994; 88 Suppl.: S1/63–S1/65

    Google Scholar 

  116. Van Thiel PPAM, van Gool T, Hopperus Buma APCC, et al. Artemisinin compounds in treatment of malaria [letter]. Lancet 1993; 341: 1034–5

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Tropical Medicine and AIDS, Department of Internal Medicine, Academic Medical Center, PO Box 22700, 1100 DE, Amsterdam, The Netherlands

    Peter J. de Vries

  2. Institute of Clinical Research in Tropical Medicine, Bach Mai Hospital, Hanoi, Vietnam

    Tran K. Dien

  3. Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands

    Tran K. Dien

Authors
  1. Peter J. de Vries
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tran K. Dien
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Vries, P.J., Dien, T.K. Clinical Pharmacology and Therapeutic Potential of Artemisinin and its Derivatives in the Treatment of Malaria. Drugs 52, 818–836 (1996). https://doi.org/10.2165/00003495-199652060-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199652060-00004

Keywords

Search

Navigation