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Artesunate

A Review of its Pharmacology and Therapeutic Efficacy in the Treatment of Malaria

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Abstract

Synopsis

Artesunate is an antimalarial agent, available in oral, rectal and parenteral formulations, that provides a rapid clinical effect in patients with Plasmodium falciparum malaria. The rapidity of effect, availability of an intravenous and intramuscular formulation and convenient dosage regimen make artesunate an ideal candidate for the treatment of severe malaria, including cerebral disease. While some results have been promising, there is no clear evidence to date that artesunate reduces mortality in patients with cerebral malaria to any greater extent than standard quinine therapy.

When given as monotherapy, treatment should be continued for at least 5 to 7 days to prevent recrudescence. Combination therapy with mefloquine allows artesunate to be administered over 3 days or less, with a satisfactory clinical outcome maintained. Although optimal dosages remain to be determined, this combination continues to provide the rapid onset of clinical effect observed with artesunate monotherapy, but decreases the rate of recrudescence to 2% (i.e. radical cure rate of 98%) when used as treatment in patients with uncomplicated malaria from areas with a high risk of multidrug-resistant falciparum malaria.

Although assessment of tolerability is complicated by the difficulty of distinguishing between disease- and treatment-related events, artesunate and artesun-ate-mefloquine combinations appear to be well tolerated in adults and children. Indeed, it is possible that prior administration of artesunate may reduce the incidence of mefloquine-induced vomiting.

Clinical findings to date have not revealed any pattern of resistance to artesunate after use of the drug. However, given the history of the development of resistance to other antimalarial drugs, the use of artesunate should be restricted to areas of multidrug resistance, the drug should be used in combination with a longer acting agent such as mefloquine, and it should be used in regimens that provide radical cure rates of 90 to 100%. If used according to these treatment principles, artesunate will provide a well tolerated and valuable addition to the current extremely limited treatment options for multidrug-resistant falciparum malaria, a widespread parasitic disease associated with considerable mortality.

Antimalarial Activity

Artesunate is an antimalarial agent which acts by increasing the oxidant stress on the intra-erythrocytic plasmodia. Although the thresholds for in vitro sensitivity and resistance of Plasmodium falciparum have not been determined, artesunate is active against chloroquine- and mefloquine-resistant strains of P. falciparum. Compared with other qinghao derivatives (arteether, artemisinin and artemether), artesunate is the most potent in vitro. The results of in vitro experiments using erythrocytes from individuals with genetic variants of α-thalassaemia indicate that artesunate is likely to be less effective in the treatment of malaria in these populations than in other patient groups; however, this has not yet been demonstrated clinically. Animal models have demonstrated the efficacy of artesunate in the treatment of experimental P. berghei infection in mice and cerebral malaria caused by P. coatneyi in rhesus monkeys.

Paired isolates from patients who had a recrudescence of infection after treatment with artesunate monotherapy, or mefloquine- or doxycycline-containing combination regimens, did not demonstrate any pattern of increased resistance in vitro to artesunate.

Pharmacokinetic Profile

The difficulty in finding an assay reliable enough to determine the plasma concentrations of the drug has limited the availability of pharmacokinetic data. In addition, interpretation of the plasma concentration-time profile for artesunate is complicated because the drug is rapidly hydrolysed to its principal active metabolite, dihydroartemisinin, and binds tightly to erythrocyte membranes. Peak plasma concentrations of artesunate and dihydroartemisinin in vivo are orders of magnitude greater than the minimum inhibitory concentration of the drug against P. falciparum in vitro. Dihydroartemisinin has a plasma elimination half-life of less than 2 hours, which may slow the development of resistance to artesunate. Artesunate has a minimal effect on hepatic cytochrome P450 activity and does not appear to influence the metabolism of mefloquine, a drug likely to be used in combination with artesunate.

Therapeutic Efficacy

Artesunate causes a rapid reduction in parasitaemia and fever in patients with falciparum malaria and is associated with an acceptable radical cure rate (i.e. >90%) if given in doses of 600mg or more (initial dose of 200mg) for 5 to 7 days. Compared with other standard antimalarial agents (mefloquine, quinine plus tetracycline and intravenous quinine), artesunate monotherapy causes a more rapid reduction in parasitaemia and fever, but actual radical cure rates have been similar in most trials.

Courses of artesunate therapy of less than 5 days commonly result in unacceptably high recrudescence rates. However, the combination of rapidly acting artesunate with mefloquine, a drug with a long elimination half-life, has been shown to be effective in preventing recrudescence. Sequential administration of various different combinations of artesunate and mefloquine has provided a rapid clinical effect, but has not always provided acceptable radical cure rates if artesunate is given over less than 2 days. This appears to be largely due to inadequate duration of artesunate treatment. Importantly, when oral artesunate 10 mg/kg was given over 3 days (initial dose of 4 mg/kg) followed by mefloquine 25 mg/kg, the regimen achieved radical cure rates of 98% in Karen patients displaced to the Myanmar-Thai border (individuals who typically are at a high risk of contracting multidrug-resistant disease). Similar sequential combination regimens were effective in patients with falciparum malaria that was unresponsive to standard therapeutic regimens. Artesunate has also been used in combination with other antimalarial agents, but to date they have all been associated with a high level of recrudescence after an initial rapid clinical effect. Preliminary data indicate that rectal administration of artesunate combined with mefloquine is effective in the treatment of both adults and children.

Because artesunate has a rapid effect and can be administered parenterally, it is an excellent choice for the treatment of cerebral malaria or other forms of severe P. falciparum malaria. Although results have been equivocal, artesunate-mefloquine combinations may reduce mortality compared with standard quinine regimens in patients with cerebral malaria. However, further clinical trials are required to substantiate these findings.

Clinically, the development of resistance to antimalarial therapy is of concern worldwide. The short elimination half-life of artesunate may favour slow development of resistance to this drug. However, general treatment principles for avoidance of resistance, such as restriction of the newer drugs to the treatment of resistant disease only and the use of regimens that provide a radical cure rate of 90 to 100%, should be applied to the use of artesunate.

Tolerability

Artesunate and other related artemisinin derivatives have been widely used in China, with no reports of any serious adverse reactions. In healthy volunteers, a reversible reduction in reticulocyte counts was the dose-limiting adverse effect of artesunate, occurring with doses of 16.88 mg/kg. Overviews of clinical studies from Thailand and China indicate that the drug is remarkably well tolerated. Possible drug-related adverse effects include dizziness, itching, vomiting and other gastrointestinal effects, reduction in neutrophil counts and convulsions. However, it is likely that many of these effects are disease-related rather than drug-induced.

When given in combination with mefloquine, artesunate has also been well tolerated. The incidence of mefloquine-induced vomiting has been variously reported to be slightly increased or markedly decreased during combination therapy: differences in the incidence of adverse effects following combination therapy may actually reflect the more rapid resolution of malarial symptoms in patients receiving the drug combination.

Of some concern is the finding that artemisinin and its derivatives cause neurotoxicity in animals; however, to date, there is no evidence of neurotoxicity occurring clinically.

Dosage and Administration

The World Health Organization (WHO) recommends that artesunate be given for a minimum of 3 days, followed sequentially by a single dose of mefloquine. If mefloquine cannot be given, then artesunate monotherapy should be given for at least 5, but preferably 7, days. A total oral artesunate dose of 600mg is recommended by some investigators for uncomplicated disease: 100 or 200mg initially then 100 mg/day for at least 4 days. If artesunate is given for less than 7 days, treatment should be followed by a therapeutic dose of mefloquine (in doses of up to 25 mg/kg depending on the degree of multidrug resistance).

For the treatment of severe disease, it is suggested that artesunate be administered intravenously or intramuscularly at an initial dose of 2 mg/kg, followed by 1 mg/kg every 12 hours until oral treatment can begin. A total administration period of 7 days is recommended. To ensure radical cure, artesunate therapy should be followed by a therapeutic dose of mefloquine.

Artesunate has shown clinical efficacy when administered rectally, but no dosage recommendations are available.

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References

  1. Rediscovering wormwood: qinghaosu for malaria [editorial]. Lancet 1992 Mar 14; 339: 649-51

  2. Klayman DL. Qinghaosu (artemisinin): an antimalarial drug from China. Science 1985 May 31; 228: 1049–55

    Article  PubMed  CAS  Google Scholar 

  3. White NJ. Antimalarial drug resistance: the pace quickens. J Antimicrob Chemother 1992; 30: 571–85

    Article  PubMed  CAS  Google Scholar 

  4. World Health Organization, editor. Practical chemotherapy of malaria: report of a WHO Scientific Group. Geneva: World Health Organization, 1990

    Google Scholar 

  5. Kozarsky PE, Lobel HO. Antimalarial agents: are we running out of options? Curr Opin Infect Dis 1994; 7: 701–7

    Article  Google Scholar 

  6. Marsh K, Forster D, Waruiru C, et al. Indicators of life-threatening malaria in African children. N Engl J Med 1995 May 25; 332(21): 1399–404

    Article  PubMed  CAS  Google Scholar 

  7. Wyler DJ. Malaria: overview and update. Clin Infect Dis 1993 Apr; 16: 449–58

    Article  PubMed  CAS  Google Scholar 

  8. Hoffman SL. Diagnosis, treatment, and prevention of malaria. Med Clin North Am 1992 Nov; 76: 1327–55

    PubMed  CAS  Google Scholar 

  9. World Health Organization, editor. International travel and health: vaccination requirements and health advice. Geneva: World Health Organization, 1995

    Google Scholar 

  10. Artesunate/mefloquine in acute uncomplicated falciparum malaria. WHO Drug Info 1993; 7 (1): 7-9

    Google Scholar 

  11. Palmer KJ, Holliday SM, Brogden RN. Mefloquine: a review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1993 Mar; 45(3): 430–75

    Article  PubMed  CAS  Google Scholar 

  12. Brasseur P, Kouamouo J, Moyou-Somo R, et al. Multi-drug resistant falciparum malaria in Cameroon in 1987-1988: II. Mefloquine resistance confirmed in vivo and in vitro and its correlation with quinine resistance. Am J Trop Med Hyg 1992; 46(1): 8–14

    PubMed  CAS  Google Scholar 

  13. Mockenhaupt FP. Mefloquine resistance in Plasmodium falciparum. Parasitol Today 1995; 11(7): 248

    Article  PubMed  CAS  Google Scholar 

  14. Artemisinin and its derivatives: use as antimalarials. WHO Drug Info 1993; 7 (3): 111-3

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

    Article  PubMed  CAS  Google Scholar 

  16. Bustos MDG, Gay F, Diquet B. In-vitro tests on Philippine isolates of Plasmodium falciparum against four standard antimalarials and four qinghaosu derivatives. Bull World Health Organ 1994; 75(5): 729–35

    Google Scholar 

  17. Kyle D, Looareesuwan S, Canfield C, et al. Susceptibility of Plasmodium falciparum in vitro to artesunate and mefloquine alone and in combination [abstract no. A-47]. Abstracts of the 92nd General Meeting of the American Society for Microbiology 1992: 8

  18. Yuthavong Y, Butthep P, Bunyaratvej A, et al. Decreased sensitivity of artesunate and chloroquine of Plasmodium falciparum infecting hemoglobin H and/or hemoglobin constant spring erythrocytes. J Clin Invest 1989 Feb; 83: 502–5

    Article  PubMed  CAS  Google Scholar 

  19. 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  PubMed  CAS  Google Scholar 

  20. Mehra N, Bhasin VK. In vitro gametocytocidal activity of artemisinin and its derivatives on Plasmodium falciparum. Jpn J Med Sci Biol 1993; 46: 37–43

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  22. 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 Dec; 49: 726–34

    PubMed  CAS  Google Scholar 

  23. Chen P-Q, Li G-Q, Guo X-B, et al. The infectivity of gametocytes of plasmodium falciparum from patients treated with artemisinin. Chin Med J 1994; 107(9): 709–11

    PubMed  CAS  Google Scholar 

  24. Pan HZ, Lin FB, Zhang ZA. Effect of sodium artesunate on malaria infected human erythrocytes. Proc Chin Acad Med Sci Peking Union Med Coll 1989; 4: 181–5

    PubMed  CAS  Google Scholar 

  25. Lin FB, Pan HZ. Peroxidative antimalaria mechanism of sodium artesunate [in Chinese]. Chung Kuo I Hsueh Ko Hsueh Yuan Hsueh Pao 1989 Jun; 11: 180–4

    CAS  Google Scholar 

  26. Meshnick SR, Tsang TW, Lin FB, et al. Activated oxygen mediates the antimalarial activity of qinghaosu. Prog Clin Biol Res 1989; 313: 95–104

    PubMed  CAS  Google Scholar 

  27. Krungkrai SR, Yuthavong Y. The antimalarial action on Plasmodium falciparum of qinghaosu and artesunate in combination with agents which modulate oxidant stress. Trans R Soc Trop Med Hyg 1987; 81: 710–4

    Article  PubMed  CAS  Google Scholar 

  28. Zhao Y, Hall IH, Oswald CB, et al. Antimalarial agents. III. Mechanism of action of artesunate against Plasmodium berghei infection. Chem Pharm Bull Tokyo 1987 May; 35: 2052–61

    Article  PubMed  CAS  Google Scholar 

  29. Zhao Y, Hanton WK, Lee KH. Antimalarial agents, 2. Artesunate, an inhibitor of cytochrome oxidase activity in Plasmodium berghei. J Nat Prod 1986 Jan-Feb; 49: 139–42

    Article  PubMed  CAS  Google Scholar 

  30. Panisko DM, Keystone JS. Treatment of malaria — 1990. Drugs 1990; 39: 160–89

    Article  PubMed  CAS  Google Scholar 

  31. Desjardins RE, Canfield CJ, Haynes JD, et al. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 1979; 16: 710–8

    Article  PubMed  CAS  Google Scholar 

  32. Rieckmann KH, Sax LJ, Campbell GH, et al. Drug sensitivity of Plasmodium falciparum: an in-vitro microtechnique. Lancet 1978; 1: 22–3

    Article  PubMed  CAS  Google Scholar 

  33. Webster HK, Boudreau EF, Pavanand K, et al. Antimalarial drug susceptibility testing of Plasmodium falciparum in Thailand using a microdilution radioisotope method. Am J Trop Med Hyg 1985; 34: 228–35

    PubMed  CAS  Google Scholar 

  34. Li J, Huang WJ. Effects of artesunate, pyronaridine and hydroxypiperaquine on chloroquine-sensitive and chloroquine-resistant isolates of Plasmodium falciparum in vitro [in Chinese]. Chung Kuo Yao Li Hsueh Pao 1988 Jan; 9: 83–6

    PubMed  CAS  Google Scholar 

  35. Yang H-L, Yang P-F, Liu D-Q, et al. Sensitivity in vitro of Plasmodium falciparum to chloroquine, pyronaridine, artesunate and piperaquine in south Yunnan [in Chinese]. Chung Kuo Chi Sheng Chung Hsueh Yu Chi Sheng Chung Ping Tsa Chih 1992; 10: 198–200

    PubMed  CAS  Google Scholar 

  36. Jiang G-F. In vitro development of sodium artesunate resistance in Plasmodium falciparum [in Chinese]. Chung Kuo Chi Sheng Chung Hsueh Yu Chi Sheng Chung Ping Tsa Chih 1992; 10: 37–9

    PubMed  CAS  Google Scholar 

  37. Chawira AN, Warhurst DC, Peters W. Qinghaosu resistance in rodent malaria. Trans R Soc Trop Med Hyg 1986; 80: 477–80

    Article  PubMed  CAS  Google Scholar 

  38. 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 Apr 4; 339: 821–4

    Article  PubMed  CAS  Google Scholar 

  39. 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 Jun; 50: 784–9

    PubMed  CAS  Google Scholar 

  40. Looareesuwan S, Viravan C, Vanijanonta S, et al. Treatment of acute uncomplicated Falciparum malaria with a short course of artesunate followed by mefloquine. Southeast Asian J Trop Med Pub Health 1993 Jun; 24: 230–4

    CAS  Google Scholar 

  41. 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 Dec; 47: 794–9

    PubMed  CAS  Google Scholar 

  42. White NJ. Antimalarial pharmacokinetics and treatment regimens. Br J Clin Pharmacol 1992; 34: 1–10

    Article  PubMed  CAS  Google Scholar 

  43. White NJ. Clinical pharmacokinetics and pharmacodynamics of artemisinin and derivatives. Trans R Soc Trop Med Hyg 1994 Jun; 88 Suppl. 1: 41–3

    Article  CAS  Google Scholar 

  44. Edlund PO, Westerlund D, Carlqvist J, et al. Determination of artesunate and dihydroartemisinine in plasma by liquid chro-matography with post-column derivatization and UV-detection. Acta Pharm Suec 1984; 21: 223–34

    PubMed  CAS  Google Scholar 

  45. Benakis A, Paris M, Plessas C, et al. Pharmacokinetics of sodium artesunate after IM and IV administration [abstract no. 415]. Am J Trop Med Hyg 1993 Sep; 49 Suppl.: 293

    Google Scholar 

  46. Li Q, Peggins JO, Masonic K, et al. Comparison of pharmacokinetics, bioavailability and hydrolysis of dihydroartemisinin, arteether, artesunate and artelinate in rats [abstract no. 298]. Am J Trop Med Hyg 1993 Sep; 49 Suppl: 243

    Google Scholar 

  47. Zhou ZM, Anders JC, Chung H, et al. Analysis of artesunic acid and dihydroqinghaosu in blood by high-performance liquid chromatography with reductive electrochemical detection. J Chromatogr 1987 Feb 20; 414: 77–90

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  50. Ye ZG, Li ZL, Li GQ, et al. Effects of qinghaosu on the surface structure of erythrocytes infected with Plasmodium berghei and the erythrocyte-free parasites. Journal of Parasites and Parasitological Disease 1986; 4: 260–2

    CAS  Google Scholar 

  51. Yang S-D, Ma J-M, Sun J-H, et al. A preliminary study on the urinary excretion of artesunate and its metabolites in man after a single intravenous injection [in Chinese]. Yao Hsueh Hsueh Pao 1987 Jun; 22: 401–4

    PubMed  CAS  Google Scholar 

  52. Bangchang KN, Karbwang J, Back DJ. Mefloquine metabolism by human liver microsomes. Effect of other antimalarial drugs. Biochem Pharmacol 1992 May 8; 43: 1957–61

    Article  PubMed  CAS  Google Scholar 

  53. Bangchang KN, Karbwang J, Back DJ. Primaquine metabolism by human liver microsomes: effect of other antimalarial drugs. Biochem Pharmacol 1992 Aug 4; 44: 587–90

    Article  PubMed  CAS  Google Scholar 

  54. Maegraith B. Malaria. In: Maegraith B, editor. Adams & Maegraith: Clinical tropical diseases. 7th ed. Oxford: Blackwell Scientific Publications, 1980: 240–92

    Google Scholar 

  55. World Health Organisation Malaria Action Programme. Severe and complicated malaria. Trans R Soc Trop Med Hyg 1986; 80 Suppl.: 1–50

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  57. Li G-Q, Guo X-B, Fu L-C, et al. A study to determine the dose of intravenous injections of artesunate in the treatment of falciparum malaria: clinical phase II. In: Li GQ, Guo X-B, Fu Y, editors. Clinical trials on qinghaosu and its derivatives, v. 1. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 44–9

    Google Scholar 

  58. 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 Sep; 22: 380–5

    CAS  Google Scholar 

  59. 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 Dec; 22: 534–8

    CAS  Google Scholar 

  60. 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 Dec; 22: 539–43

    CAS  Google Scholar 

  61. Guo X-B, Fu L-C, Fan T-T, et al. Thirty three patients with cerebral malaria treated with intravenous artesunate. In: Li GQ, Guo X-B, Fu Y, editors. Clinical trials on qinghaosu and its derivatives, v. 1. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 59–63

    Google Scholar 

  62. Li GQ, Guo XB, Jin R, et al. Clinical studies on treatment of cerebral malaria with qinghaosu and its derivatives. J Tradit Chin Med 1982 Jun; 2: 125–30

    PubMed  CAS  Google Scholar 

  63. Li G-Q, Guo X-B, Fu L-C. A randomised comparative study of artesunate versus quinine dihydrochloride in the treatment of falciparum malaria. In: Li GQ, Guo X-B, Yang F, editors. Clinical trials on qinghaosu and its derivatives. v. 1. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 50–8

    Google Scholar 

  64. Karbwang J, Na-Bangchang K, Thanavibul A, et al. Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria. Bull World Health Organ 1994; 72(2): 233–8

    PubMed  CAS  Google Scholar 

  65. Li G-Q, Guo XB, Fu L-C, et al. A summary of the clinical studies on artesunate intravenous injection in malaria patients. In: Li GQ, Guo X-B, Fu Y, editors. Clinical trials on qinghaosu and its derivatives. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 1–7

    Google Scholar 

  66. Li G-Q, Guo X-B, Fu L-C, et al. Clinical trials of artemisinin and its derivatives in the treatment of malaria in China. Trans R Soc Trop Med Hyg 1994 Jun; 88 Suppl. 1: 5–6

    Article  Google Scholar 

  67. China Cooperative Research Group on Qinghaosu and its Derivatives as Antimalarials. Clinical studies on the treatment of malaria with qinghaosu and its derivatives. Journal of Traditional Chinese Medicine 1982; 2(1): 45–50

    Google Scholar 

  68. Looareesuwan S, Vanijanonta S, Viravan C, et al. Randomized trial of mefloquine alone and artesunate followed by mefloquine for the treatment of acute uncomplicated falciparum malaria. Ann Trop Med Parasitol 1994 Apr; 88: 131–6

    PubMed  CAS  Google Scholar 

  69. Karbwang J, Na-Bangchang K, Thanavibul A, et al. Pharmacokinetics of mefloquine alone or in combination with artesunate. Bull World Health Organ 1994; 72: 83–7

    PubMed  CAS  Google Scholar 

  70. Luxemburger C, Nosten F, Shotar, et al. Oral artesunate in the treatment of uncomplicated hyperparasitaemic falciparum malaria. Am J Trop Med Hyg. In press

  71. 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(6): 777–82

    PubMed  CAS  Google Scholar 

  72. 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 Nov-Dec; 86: 582–3

    Article  PubMed  CAS  Google Scholar 

  73. Fu L-C, Guo X-B, Fu Y-X, et al. Clinical studies on the treatment of falciparum malaria with artesunate intramuscular injection and a randomly controlled study on artesunate and piperaquine. In: Li GQ, Guo X-B, Yang F, editors. Clinical trials on qinghaosu and its derivatives. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 66–71

    Google Scholar 

  74. Guo X-B, Fu Y-X, Chen P-Q, et al. A randomised comparative study on the treatment of falciparum malaria with artesunate tablets and piperaquine. In: Li GQ, Guo X-B, Yang F, editors. Clinical trials on qinghaosu and its derivatives. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 72–7

    Google Scholar 

  75. Smithuis FM, van Woensel JBM, Nordlander E, et al. Comparison of two mefloquine regimens for treatment of Plasmodium falciparum malaria on the northeastern Thai-Cambodian border. Antimicrob Agents Chemother 1993 Sept; 37(9): 1977–81

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  77. van Thiel PP, van Gool T, Hopperus-Buma AP, et al. Artemisinin compounds in treatment of malaria [letter; comment]. Lancet 1993 Apr 17; 341: 1034–5

    Article  PubMed  Google Scholar 

  78. Chawira AN, Warhurst DC. The effect of artemisinin combined with standard antimalarials against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro. J Trop Med Hyg 1987; 90: 1–8

    PubMed  CAS  Google Scholar 

  79. Chawira AN, Warhurst DC, Robinson BL, et al. The effect of combinations of qinghaosu (artemisinin) with standard anti-malarial drugs in the suppressive treatment of malaria in mice. Trans R Soc Trop Med Hyg 1987; 81: 554–8

    Article  PubMed  CAS  Google Scholar 

  80. Looareesuwan S, Harinasuta T, Chongsuphajaisiddhi T. Drug resistant malaria, with special reference to Thailand. Southeast Asian J Trop Med Pub Health 1992 Dec; 23(4): 621–34

    CAS  Google Scholar 

  81. White NJ, Pukrittayakamee S. Clinical malaria in the tropics. Med J Aust 1993 Aug 2; 159: 197–203

    PubMed  CAS  Google Scholar 

  82. Trevett A, Lalloo D. A new look at an old drug: artemesinin and qinghaosu. PNG Med J 1992 Dec; 35: 264–9

    CAS  Google Scholar 

  83. 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 Nov-Dec; 86: 584–5

    Article  PubMed  CAS  Google Scholar 

  84. Nosten F, Price RN. New antimalarials: a risk-benefit analysis. Drug Saf 1995 Apr; 12(4): 264–73

    Article  PubMed  CAS  Google Scholar 

  85. Wesche DL, DeCoster MA, Tortella FC, et al. Neurotoxicity of artemisinin analogs in vitro. Antimicrob Agents Chemother 1994 Aug; 38(8): 1813–9

    Article  PubMed  CAS  Google Scholar 

  86. Brewer TG, Petras JM, Peggins JO, et al. Differential neurotoxicity of artemesinin analogs in an in vivo model [abstract no. 413]. American Society of Tropical Medicine and Hygiene and the American Society of Parasitologists; 1993 Oct 31-Nov 4; Atlanta, Georgia, 292.

  87. Guo X-B, Fu L-C, Yu C-G, et al. A study on tolerance and toxic side-effects of artesunate intravenous injection on healthy volunteers: clinical trials phase I. In: Li GQ, Guo X-B, Fu Y, editors. Clinical trials on qinghaosu and its derivatives, v. 1. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 39–43

    Google Scholar 

  88. Looareesuwan S. Overview of clinical studies on artemisinin derivatives in Thailand. Trans R Soc Trop Med Hyg 1994 Jun; 88 Suppl. 1: 9–11

    Article  Google Scholar 

  89. Nosten F. Artemisinin: large community studies. Trans R Soc Trop Med Hyg 1994 Jun; 88 Suppl. 1: 45–6

    Article  Google Scholar 

  90. Hien TT, White NJ. Qinghaosu. Lancet 1993 Mar 6; 341: 603–8

    Article  PubMed  CAS  Google Scholar 

  91. 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. In: Li GQ, Guo X-B, Fu Y, editors. Clinical trials on qinghaosu and its derivatives. v. 1. Guangzhou: Guangzhou College of Traditional Chinese Medicine Sanya Tropical Medicine Institute, 1990: 86

    Google Scholar 

  92. China Cooperative Research Group on Qinghaosu and its Derivatives as Antimalarials. Studies on the toxicity of qinghaosu and its derivatives. Journal of Traditional Chinese Medicine 1982; 2(1): 31–8

    Google Scholar 

  93. White NJ. Artemisinin: current status. Trans R Soc Trop Med Hyg 1994 Jun; 88 Suppl. 1: 3–4

    Article  Google Scholar 

  94. Batty KT, Ilett KF, Davis TME. Chemical stability of artesunic acid injection, a new antimalarial drug derived from qinghaosu [abstract no. 2]. Aust J Hosp Pharm 1995; 25: 100

    Google Scholar 

  95. Arnold K. Qinghaosu in malaria: hope or hazard? Presented at Tropical Medicine Update: a bench to bedside perspective on new and reemerging tropical infectious diseases, Oct 30-31, Atlanta, Georgia, 1993.

  96. Bia FJ. Medical considerations for the pregnant traveler. Infect Dis Clin North Am 1992 Jun; 6(2): 371–88

    PubMed  CAS  Google Scholar 

  97. World Health Organization, editor. WHO model prescribing information: drugs used in parasitic diseases. Geneva: World Health Organization, 1990

    Google Scholar 

  98. Am NT. Malaria in Viet-nam: environment, prevention and treatment [in French]. Bull Soc Pathol Exot 1993; 86: 494–9

    Google Scholar 

  99. Schapira A, Beales PF, Halloran ME. Malaria: living with drug resistance. Parasitol Today 1993; 9(5): 168–74

    Article  PubMed  CAS  Google Scholar 

  100. Hien TT, Arnold KL, Hung NT, et al. Single dose artemisininmefloquine treatment for acute uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 1994; 88: 688–91

    Article  Google Scholar 

  101. 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. In press

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Various sections of the manuscript reviewed by: K. Arnold, Intensive Care Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Vietnam; G.C. Cook, Hospital for Tropical Diseases, London, England; D.E. Davidson, Product Development Unit, World Health Organization Special Programme for Research and Training in Tropical Diseases; World Health Organization, Geneva, Switzerland; T.T. Hien, Intensive Care Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Vietnam; S. Hoffman, Malaria Program, Naval Medical Research Institute, Bethesda, Maryland, USA; N. Kumar, Department of Immunology and Infectious Diseases, The Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland, USA; G.-Q. Li, Sanya Tropical Medicine Institute, Guangzhou College of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; S. Looareesuwan, Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; F. Nosten, Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; R. Price, Shoklo Malaria Research Unit, Mae Sot, Tak Province, Thailand; P.P.A.M. van Thiel, Department of Infectious Diseases, Tropical Medicine and AIDS, Amsterdam, The Netherlands; D. Warhurst, Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, England; N.J. White, University of Oxford, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford, England; R. Wise, Department of Medical Microbiology, Dudley Road Hospital, Birmingham, England.

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Barradell, L.B., Fitton, A. Artesunate. Drugs 50, 714–741 (1995). https://doi.org/10.2165/00003495-199550040-00009

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