Skip to main content
PMC home page
Postgraduate Medical Journal logoLink to Postgraduate Medical Journal
. 2005 Feb;81(952):71–78. doi: 10.1136/pgmj.2004.028399

Artemisinins

C Woodrow 1, R Haynes 1, S Krishna 1
PMCID: PMC1743191  PMID: 15701735

Abstract

Artemisinins were discovered to be highly effective antimalarial drugs shortly after the isolation of the parent artemisinin in 1971 in China. These compounds combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. Artemisinin containing regimens meet the urgent need to find effective treatments for multidrug resistant malaria and have recently been advocated for widespread deployment. Comparative trials of artesunate and quinine for severe malaria are in progress to see if the persistently high mortality of this condition can be reduced.

Full Text

The Full Text of this article is available as a PDF (110.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adjuik M., Babiker A., Garner P., Olliaro P., Taylor W., White N., International Artemisinin Study Group Artesunate combinations for treatment of malaria: meta-analysis. Lancet. 2004 Jan 3;363(9402):9–17. doi: 10.1016/s0140-6736(03)15162-8. [DOI] [PubMed] [Google Scholar]
  2. Agbenyega T., Angus B. J., Bedu-Addo G., Baffoe-Bonnie B., Guyton T., Stacpoole P. W., Krishna S. Glucose and lactate kinetics in children with severe malaria. J Clin Endocrinol Metab. 2000 Apr;85(4):1569–1576. doi: 10.1210/jcem.85.4.6529. [DOI] [PubMed] [Google Scholar]
  3. Angus B. J., Chotivanich K., Udomsangpetch R., White N. J. In vivo removal of malaria parasites from red blood cells without their destruction in acute falciparum malaria. Blood. 1997 Sep 1;90(5):2037–2040. [PubMed] [Google Scholar]
  4. Angus Brian J., Thaiaporn Itaporn, Chanthapadith Kenechanh, Suputtamongkol Yupin, White Nicholas J. Oral artesunate dose-response relationship in acute falciparum malaria. Antimicrob Agents Chemother. 2002 Mar;46(3):778–782. doi: 10.1128/AAC.46.3.778-782.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arnold K., Tran T. H., Nguyen T. C., Nguyen H. P., Pham P. A randomized comparative study of artemisinine (qinghaosu) suppositories and oral quinine in acute falciparum malaria. Trans R Soc Trop Med Hyg. 1990 Jul-Aug;84(4):499–502. doi: 10.1016/0035-9203(90)90012-4. [DOI] [PubMed] [Google Scholar]
  6. Ashton M., Nguyen D. S., Nguyen V. H., Gordi T., Trinh N. H., Dinh X. H., Nguyen T. N., Le D. C. Artemisinin kinetics and dynamics during oral and rectal treatment of uncomplicated malaria. Clin Pharmacol Ther. 1998 Apr;63(4):482–493. doi: 10.1016/S0009-9236(98)90044-3. [DOI] [PubMed] [Google Scholar]
  7. Barennes H., Sterlingot H., Nagot N., Meda H., Kaboré M., Sanou M., Nacro B., Bourée P., Pussard E. Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria. Eur J Clin Pharmacol. 2003 Jan 29;58(10):649–652. doi: 10.1007/s00228-002-0546-2. [DOI] [PubMed] [Google Scholar]
  8. Barnes K. I., Mwenechanya J., Tembo M., McIlleron H., Folb P. I., Ribeiro I., Little F., Gomes M., Molyneux M. E. Efficacy of rectal artesunate compared with parenteral quinine in initial treatment of moderately severe malaria in African children and adults: a randomised study. Lancet. 2004 May 15;363(9421):1598–1605. doi: 10.1016/S0140-6736(04)16203-X. [DOI] [PubMed] [Google Scholar]
  9. Batty K. T., Thu L. T., Davis T. M., Ilett K. F., Mai T. X., Hung N. C., Tien N. P., Powell S. M., Thien H. V., Binh T. Q. A pharmacokinetic and pharmacodynamic study of intravenous vs oral artesunate in uncomplicated falciparum malaria. Br J Clin Pharmacol. 1998 Feb;45(2):123–129. doi: 10.1046/j.1365-2125.1998.00655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Batty Kevin T., Ilett Kenneth F., Davis Timothy M. E. Protein binding and alpha : beta anomer ratio of dihydroartemisinin in vivo. Br J Clin Pharmacol. 2004 Apr;57(4):529–533. doi: 10.1046/j.1365-2125.2003.02045.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Benakis A., Paris M., Loutan L., Plessas C. T., Plessas S. T. Pharmacokinetics of artemisinin and artesunate after oral administration in healthy volunteers. Am J Trop Med Hyg. 1997 Jan;56(1):17–23. doi: 10.4269/ajtmh.1997.56.17. [DOI] [PubMed] [Google Scholar]
  12. Bethell D. B., Teja-Isavadharm P., Cao X. T., Pham T. T., Ta T. T., Tran T. N., Nguyen T. T., Pham T. P., Kyle D., Day N. P. Pharmacokinetics of oral artesunate in children with moderately severe Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 1997 Mar-Apr;91(2):195–198. doi: 10.1016/s0035-9203(97)90222-4. [DOI] [PubMed] [Google Scholar]
  13. Binh T. Q., Ilett K. F., Batty K. T., Davis T. M., Hung N. C., Powell S. M., Thu L. T., Thien H. V., Phuöng H. L., Phuong V. D. Oral bioavailability of dihydroartemisinin in Vietnamese volunteers and in patients with falciparum malaria. Br J Clin Pharmacol. 2001 Jun;51(6):541–546. doi: 10.1046/j.1365-2125.2001.01395.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Borrmann Steffen, Szlezák Nicole, Binder Ronald K., Missinou Michel A., Lell Bertrand, Kremsner Peter G. Evidence for the efficacy of artesunate in asymptomatic Plasmodium malariae infections. J Antimicrob Chemother. 2002 Nov;50(5):751–754. doi: 10.1093/jac/dkf200. [DOI] [PubMed] [Google Scholar]
  15. Brewer T. G., Grate S. J., Peggins J. O., Weina P. J., Petras J. M., Levine B. S., Heiffer M. H., Schuster B. G. Fatal neurotoxicity of arteether and artemether. Am J Trop Med Hyg. 1994 Sep;51(3):251–259. doi: 10.4269/ajtmh.1994.51.251. [DOI] [PubMed] [Google Scholar]
  16. Brewer T. G., Peggins J. O., Grate S. J., Petras J. M., Levine B. S., Weina P. J., Swearengen J., Heiffer M. H., Schuster B. G. Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg. 1994 Jun;88 (Suppl 1):S33–S36. doi: 10.1016/0035-9203(94)90469-3. [DOI] [PubMed] [Google Scholar]
  17. Brockman A., Price R. N., van Vugt M., Heppner D. G., Walsh D., Sookto P., Wimonwattrawatee T., Looareesuwan S., White N. J., Nosten F. Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine. Trans R Soc Trop Med Hyg. 2000 Sep-Oct;94(5):537–544. doi: 10.1016/s0035-9203(00)90080-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cao X. T., Bethell D. B., Pham T. P., Ta T. T., Tran T. N., Nguyen T. T., Pham T. T., Nguyen T. T., Day N. P., White N. J. Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria. Trans R Soc Trop Med Hyg. 1997 May-Jun;91(3):335–342. doi: 10.1016/s0035-9203(97)90099-7. [DOI] [PubMed] [Google Scholar]
  19. Clark I. A., Hunt N. H., Cowden W. B., Maxwell L. E., Mackie E. J. Radical-mediated damage to parasites and erythrocytes in Plasmodium vinckei infected mice after injection of t-butyl hydroperoxide. Clin Exp Immunol. 1984 Jun;56(3):524–530. [PMC free article] [PubMed] [Google Scholar]
  20. Davis T. M., Phuong H. L., Ilett K. F., Hung N. C., Batty K. T., Phuong V. D., Powell S. M., Thien H. V., Binh T. Q. Pharmacokinetics and pharmacodynamics of intravenous artesunate in severe falciparum malaria. Antimicrob Agents Chemother. 2001 Jan;45(1):181–186. doi: 10.1128/AAC.45.1.181-186.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. De Vries P. J., Tran K. D., Nguyen X. K., Le Nguyen B., Pham T. Y., Dao D. D., Van Boxtel C. J., Kager P. A. The pharmacokinetics of a single dose of artemisinin in patients with uncomplicated falciparum malaria. Am J Trop Med Hyg. 1997 May;56(5):503–507. doi: 10.4269/ajtmh.1997.56.503. [DOI] [PubMed] [Google Scholar]
  22. Deen J. L., von Seidlein L., Pinder M., Walraven G. E., Greenwood B. M. The safety of the combination artesunate and pyrimethamine-sulfadoxine given during pregnancy. Trans R Soc Trop Med Hyg. 2001 Jul-Aug;95(4):424–428. doi: 10.1016/s0035-9203(01)90204-4. [DOI] [PubMed] [Google Scholar]
  23. Dorsey Grant, Vlahos Jonathan, Kamya Moses R., Staedke Sarah G., Rosenthal Philip J. Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria. J Infect Dis. 2003 Oct 10;188(8):1231–1238. doi: 10.1086/378523. [DOI] [PubMed] [Google Scholar]
  24. Eckstein-Ludwig U., Webb R. J., Van Goethem I. D. A., East J. M., Lee A. G., Kimura M., O'Neill P. M., Bray P. G., Ward S. A., Krishna S. Artemisinins target the SERCA of Plasmodium falciparum. Nature. 2003 Aug 21;424(6951):957–961. doi: 10.1038/nature01813. [DOI] [PubMed] [Google Scholar]
  25. Eckstein-Ludwig U., Webb R. J., Van Goethem I. D. A., East J. M., Lee A. G., Kimura M., O'Neill P. M., Bray P. G., Ward S. A., Krishna S. Artemisinins target the SERCA of Plasmodium falciparum. Nature. 2003 Aug 21;424(6951):957–961. doi: 10.1038/nature01813. [DOI] [PubMed] [Google Scholar]
  26. Efferth Thomas, Sauerbrey Axel, Olbrich Armin, Gebhart Erich, Rauch Pia, Weber H. Oliver, Hengstler Jan G., Halatsch Marc-Eric, Volm Manfred, Tew Kenneth D. Molecular modes of action of artesunate in tumor cell lines. Mol Pharmacol. 2003 Aug;64(2):382–394. doi: 10.1124/mol.64.2.382. [DOI] [PubMed] [Google Scholar]
  27. Giao P. T., Binh T. Q., Kager P. A., Long H. P., Van Thang N., Van Nam N., de Vries P. J. Artemisinin for treatment of uncomplicated falciparum malaria: is there a place for monotherapy? Am J Trop Med Hyg. 2001 Dec;65(6):690–695. doi: 10.4269/ajtmh.2001.65.690. [DOI] [PubMed] [Google Scholar]
  28. Giao P. T., Binh T. Q., Kager P. A., Long H. P., Van Thang N., Van Nam N., de Vries P. J. Artemisinin for treatment of uncomplicated falciparum malaria: is there a place for monotherapy? Am J Trop Med Hyg. 2001 Dec;65(6):690–695. doi: 10.4269/ajtmh.2001.65.690. [DOI] [PubMed] [Google Scholar]
  29. Giao P. T., de Vries P. J. Pharmacokinetic interactions of antimalarial agents. Clin Pharmacokinet. 2001;40(5):343–373. doi: 10.2165/00003088-200140050-00003. [DOI] [PubMed] [Google Scholar]
  30. Gordi Toufigh, Lepist Eve Irene. Artemisinin derivatives: toxic for laboratory animals, safe for humans? Toxicol Lett. 2004 Mar 1;147(2):99–107. doi: 10.1016/j.toxlet.2003.12.009. [DOI] [PubMed] [Google Scholar]
  31. Gordi Toufigh, Lepist Eve Irene. Artemisinin derivatives: toxic for laboratory animals, safe for humans? Toxicol Lett. 2004 Mar 1;147(2):99–107. doi: 10.1016/j.toxlet.2003.12.009. [DOI] [PubMed] [Google Scholar]
  32. Ha V., Nguyen N. H., Tran T. B., Bui M. C., Nguyen H. P., Tran T. H., Phan T. Q., Arnold K., Tran T. H. Severe and complicated malaria treated with artemisinin, artesunate or artemether in Viet Nam. Trans R Soc Trop Med Hyg. 1997 Jul-Aug;91(4):465–467. doi: 10.1016/s0035-9203(97)90287-x. [DOI] [PubMed] [Google Scholar]
  33. Halpaap B., Ndjave M., Paris M., Benakis A., Kremsner P. G. Plasma levels of artesunate and dihydroartemisinin in children with Plasmodium falciparum malaria in Gabon after administration of 50-milligram artesunate suppositories. Am J Trop Med Hyg. 1998 Mar;58(3):365–368. doi: 10.4269/ajtmh.1998.58.365. [DOI] [PubMed] [Google Scholar]
  34. Hassan Alin M., Ashton M., Kihamia C. M., Mtey G. J., Björkman A. 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 Jan-Feb;90(1):61–65. doi: 10.1016/s0035-9203(96)90480-0. [DOI] [PubMed] [Google Scholar]
  35. Haynes R. K. Artemisinin and derivatives: the future for malaria treatment? Curr Opin Infect Dis. 2001 Dec;14(6):719–726. doi: 10.1097/00001432-200112000-00010. [DOI] [PubMed] [Google Scholar]
  36. Haynes Richard K., Krishna Sanjeev. Artemisinins: activities and actions. Microbes Infect. 2004 Nov;6(14):1339–1346. doi: 10.1016/j.micinf.2004.09.002. [DOI] [PubMed] [Google Scholar]
  37. Hien T. T., Phu N. H., Mai N. T., Chau T. T., Trang T. T., Loc P. P., Cuong B. M., Dung N. T., Vinh H., Waller D. J. An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria. Trans R Soc Trop Med Hyg. 1992 Nov-Dec;86(6):584–585. doi: 10.1016/0035-9203(92)90138-3. [DOI] [PubMed] [Google Scholar]
  38. Hien T. T., Turner G. D. H., Mai N. T. H., Phu N. H., Bethell D., Blakemore W. F., Cavanagh J. B., Dayan A., Medana I., Weller R. O. Neuropathological assessment of artemether-treated severe malaria. Lancet. 2003 Jul 26;362(9380):295–296. doi: 10.1016/s0140-6736(03)13974-8. [DOI] [PubMed] [Google Scholar]
  39. Hien T. T., White N. J. Qinghaosu. Lancet. 1993 Mar 6;341(8845):603–608. doi: 10.1016/0140-6736(93)90362-k. [DOI] [PubMed] [Google Scholar]
  40. Ilett Kenneth F., Batty Kevin T., Powell Shane M., Binh Tran Quang, Thu Le Thi Anh, Phuong Hoang Lan, Hung Nguyen Canh, Davis Timothy M. E. The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria. Br J Clin Pharmacol. 2002 Jan;53(1):23–30. doi: 10.1046/j.0306-5251.2001.01519.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Karbwang J., Na-Bangchang K., Tin T., Sukontason K., Rimchala W., Harinasuta T. Pharmacokinetics of intramuscular artemether in patients with severe falciparum malaria with or without acute renal failure. Br J Clin Pharmacol. 1998 Jun;45(6):597–600. doi: 10.1046/j.1365-2125.1998.00723.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Karbwang J., Na-Bangchang K., Wattanakoon Y., Thanavibul A., Harinasuta T. Artemether 5 versus 7 day regimen for severe falciparum malaria. Southeast Asian J Trop Med Public Health. 1994 Dec;25(4):702–706. [PubMed] [Google Scholar]
  43. Karbwang J., Tin T., Rimchala W., Sukontason K., Namsiripongpun V., Thanavibul A., Na-Bangchang K., Laothavorn P., Bunnag D., Harinasuta T. Comparison of artemether and quinine in the treatment of severe falciparum malaria in south-east Thailand. Trans R Soc Trop Med Hyg. 1995 Nov-Dec;89(6):668–671. doi: 10.1016/0035-9203(95)90437-9. [DOI] [PubMed] [Google Scholar]
  44. Karunajeewa Harin A., Ilett Kenneth F., Dufall Kitiya, Kemiki Adedayo, Bockarie Moses, Alpers Michael P., Barrett P. Hugh, Vicini Paolo, Davis Timothy M. E. Disposition of artesunate and dihydroartemisinin after administration of artesunate suppositories in children from Papua New Guinea with uncomplicated malaria. Antimicrob Agents Chemother. 2004 Aug;48(8):2966–2972. doi: 10.1128/AAC.48.8.2966-2972.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Khanh N. X., de Vries P. J., Ha L. D., van Boxtel C. J., Koopmans R., Kager P. A. Declining concentrations of dihydroartemisinin in plasma during 5-day oral treatment with artesunate for Falciparum malaria. Antimicrob Agents Chemother. 1999 Mar;43(3):690–692. doi: 10.1128/aac.43.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kissinger E., Hien T. T., Hung N. T., Nam N. D., Tuyen N. L., Dinh B. V., Mann C., Phu N. H., Loc P. P., Simpson J. A. Clinical and neurophysiological study of the effects of multiple doses of artemisinin on brain-stem function in Vietnamese patients. Am J Trop Med Hyg. 2000 Jul-Aug;63(1-2):48–55. doi: 10.4269/ajtmh.2000.63.48. [DOI] [PubMed] [Google Scholar]
  47. Koopmans R., Duc D. D., Kager P. A., Khanh N. X., Dien T. K., de Vries P. J., van Boxtel C. J. The pharmacokinetics of artemisinin suppositories in Vietnamese patients with malaria. Trans R Soc Trop Med Hyg. 1998 Jul-Aug;92(4):434–436. doi: 10.1016/s0035-9203(98)91082-3. [DOI] [PubMed] [Google Scholar]
  48. Koopmans R., Ha L. D., Duc D. D., Dien T. K., Kager P. A., Khanh N. X., van Boxtel C. J., De Vries P. J. The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects. Am J Trop Med Hyg. 1999 Feb;60(2):244–247. doi: 10.4269/ajtmh.1999.60.244. [DOI] [PubMed] [Google Scholar]
  49. Kremsner Peter Gottfried, Krishna Sanjeev. Antimalarial combinations. Lancet. 2004 Jul 17;364(9430):285–294. doi: 10.1016/S0140-6736(04)16680-4. [DOI] [PubMed] [Google Scholar]
  50. Krishna S., Planche T., Agbenyega T., Woodrow C., Agranoff D., Bedu-Addo G., Owusu-Ofori A. K., Appiah J. A., Ramanathan S., Mansor S. M. Bioavailability and preliminary clinical efficacy of intrarectal artesunate in Ghanaian children with moderate malaria. Antimicrob Agents Chemother. 2001 Feb;45(2):509–516. doi: 10.1128/AAC.45.2.509-516.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Krishna Sanjeev, Uhlemann Anne-Catrin, Haynes Richard K. Artemisinins: mechanisms of action and potential for resistance. Drug Resist Updat. 2004 Aug-Oct;7(4-5):233–244. doi: 10.1016/j.drup.2004.07.001. [DOI] [PubMed] [Google Scholar]
  52. Kumar N., Zheng H. Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. Parasitol Res. 1990;76(3):214–218. doi: 10.1007/BF00930817. [DOI] [PubMed] [Google Scholar]
  53. Leonardi E., Gilvary G., White N. J., Nosten F. Severe allergic reactions to oral artesunate: a report of two cases. Trans R Soc Trop Med Hyg. 2001 Mar-Apr;95(2):182–183. doi: 10.1016/s0035-9203(01)90157-9. [DOI] [PubMed] [Google Scholar]
  54. Li G. Q., Guo X. B., Fu L. C., Jian H. X., Wang X. H. 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):S5–S6. doi: 10.1016/0035-9203(94)90460-x. [DOI] [PubMed] [Google Scholar]
  55. Li Q. G., Brueckner R. P., Peggins J. O., Trotman K. M., Brewer T. G. Arteether toxicokinetics and pharmacokinetics in rats after 25 mg/kg/day single and multiple doses. Eur J Drug Metab Pharmacokinet. 1999 Jul-Sep;24(3):213–223. doi: 10.1007/BF03190023. [DOI] [PubMed] [Google Scholar]
  56. Li Q. G., Peggins J. O., Fleckenstein L. L., Masonic K., Heiffer M. H., Brewer T. G. The pharmacokinetics and bioavailability of dihydroartemisinin, arteether, artemether, artesunic acid and artelinic acid in rats. J Pharm Pharmacol. 1998 Feb;50(2):173–182. doi: 10.1111/j.2042-7158.1998.tb06173.x. [DOI] [PubMed] [Google Scholar]
  57. Looareesuwan S., Oosterhuis B., Schilizzi B. M., Sollie F. A. E., Wilairatana P., Krudsood S., Lugt Ch B., Peeters P. A. M., Peggins J. O. Dose-finding and efficacy study for i.m. artemotil (beta-arteether) and comparison with i.m. artemether in acute uncomplicated P. falciparum malaria. Br J Clin Pharmacol. 2002 May;53(5):492–500. doi: 10.1046/j.1365-2125.2002.01590.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Looareesuwan S., Vanijanonta S., Viravan C., Wilairatana P., Charoenlarp P., Andrial M. 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(2):131–136. doi: 10.1080/00034983.1994.11812850. [DOI] [PubMed] [Google Scholar]
  59. McGready R., Cho T., Keo N. K., Thwai K. L., Villegas L., Looareesuwan S., White N. J., Nosten F. Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis. 2001 Nov 9;33(12):2009–2016. doi: 10.1086/324349. [DOI] [PubMed] [Google Scholar]
  60. Meshnick S. R., Thomas A., Ranz A., Xu C. M., Pan H. Z. Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action. Mol Biochem Parasitol. 1991 Dec;49(2):181–189. doi: 10.1016/0166-6851(91)90062-b. [DOI] [PubMed] [Google Scholar]
  61. Mithwani Sadik, Aarons Leon, Kokwaro Gilbert O., Majid Oneeb, Muchohi Simon, Edwards Geoffrey, Mohamed Sumia, Marsh Kevin, Watkins William. Population pharmacokinetics of artemether and dihydroartemisinin following single intramuscular dosing of artemether in African children with severe falciparum malaria. Br J Clin Pharmacol. 2004 Feb;57(2):146–152. doi: 10.1046/j.1365-2125.2003.01986.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Murphy S. A., Mberu E., Muhia D., English M., Crawley J., Waruiru C., Lowe B., Newton C. R., Winstanley P., Marsh K. The disposition of intramuscular artemether in children with cerebral malaria; a preliminary study. Trans R Soc Trop Med Hyg. 1997 May-Jun;91(3):331–334. doi: 10.1016/s0035-9203(97)90097-3. [DOI] [PubMed] [Google Scholar]
  63. Murphy S., English M., Waruiru C., Mwangi I., Amukoye E., Crawley J., Newton C., Winstanley P., Peshu N., Marsh K. An open randomized trial of artemether versus quinine in the treatment of cerebral malaria in African children. Trans R Soc Trop Med Hyg. 1996 May-Jun;90(3):298–301. doi: 10.1016/s0035-9203(96)90260-6. [DOI] [PubMed] [Google Scholar]
  64. Na-Bangchang K., Karbwang J., Congpoung K., Thanavibul A., Ubalee R. Pharmacokinetic and bioequivalence evaluation of two generic formulations of oral artesunate. Eur J Clin Pharmacol. 1998 Jan;53(5):375–376. doi: 10.1007/s002280050397. [DOI] [PubMed] [Google Scholar]
  65. Navaratnam V., Mansor S. M., Mordi M. N., Akbar A., Abdullah M. N. Comparative pharmacokinetic study of oral and rectal formulations of artesunic acid in healthy volunteers. Eur J Clin Pharmacol. 1998 Jul;54(5):411–414. doi: 10.1007/s002280050484. [DOI] [PubMed] [Google Scholar]
  66. Navaratnam V., Mansor S. M., Sit N. W., Grace J., Li Q., Olliaro P. Pharmacokinetics of artemisinin-type compounds. Clin Pharmacokinet. 2000 Oct;39(4):255–270. doi: 10.2165/00003088-200039040-00002. [DOI] [PubMed] [Google Scholar]
  67. Nealon Claire, Dzeing Arnaud, Müller-Römer Ulrich, Planche Timothy, Sinou Veronique, Kombila Maryvonne, Kremsner Peter G., Parzy Daniel, Krishna Sanjeev. Intramuscular bioavailability and clinical efficacy of artesunate in gabonese children with severe malaria. Antimicrob Agents Chemother. 2002 Dec;46(12):3933–3939. doi: 10.1128/AAC.46.12.3933-3939.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Newton C. R., Krishna S. Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther. 1998 Jul;79(1):1–53. doi: 10.1016/s0163-7258(98)00008-4. [DOI] [PubMed] [Google Scholar]
  69. Newton P., Proux S., Green M., Smithuis F., Rozendaal J., Prakongpan S., Chotivanich K., Mayxay M., Looareesuwan S., Farrar J. Fake artesunate in southeast Asia. Lancet. 2001 Jun 16;357(9272):1948–1950. doi: 10.1016/S0140-6736(00)05085-6. [DOI] [PubMed] [Google Scholar]
  70. Newton P., Suputtamongkol Y., Teja-Isavadharm P., Pukrittayakamee S., Navaratnam V., Bates I., White N. Antimalarial bioavailability and disposition of artesunate in acute falciparum malaria. Antimicrob Agents Chemother. 2000 Apr;44(4):972–977. doi: 10.1128/aac.44.4.972-977.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Newton Paul N., van Vugt Michele, Teja-Isavadharm Paktiya, Siriyanonda Duangsuda, Rasameesoroj Maneerat, Teerapong Pramote, Ruangveerayuth Ronatrai, Slight Thra, Nosten Francois, Suputtamongkol Yupin. Comparison of oral artesunate and dihydroartemisinin antimalarial bioavailabilities in acute falciparum malaria. Antimicrob Agents Chemother. 2002 Apr;46(4):1125–1127. doi: 10.1128/AAC.46.4.1125-1127.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Nosten F., Luxemburger C., ter Kuile F. O., Woodrow C., Eh J. P., Chongsuphajaisiddhi T., White N. J. Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. J Infect Dis. 1994 Oct;170(4):971–977. doi: 10.1093/infdis/170.4.971. [DOI] [PubMed] [Google Scholar]
  73. Nosten F., ter Kuile F., Chongsuphajaisiddhi T., Luxemburger C., Webster H. K., Edstein M., Phaipun L., Thew K. L., White N. J. Mefloquine-resistant falciparum malaria on the Thai-Burmese border. Lancet. 1991 May 11;337(8750):1140–1143. doi: 10.1016/0140-6736(91)92798-7. [DOI] [PubMed] [Google Scholar]
  74. O'Neill Paul M., Posner Gary H. A medicinal chemistry perspective on artemisinin and related endoperoxides. J Med Chem. 2004 Jun 3;47(12):2945–2964. doi: 10.1021/jm030571c. [DOI] [PubMed] [Google Scholar]
  75. Olliaro P. L., Taylor W. R. Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review. J Postgrad Med. 2004 Jan-Mar;50(1):40–44. [PubMed] [Google Scholar]
  76. Orjih A. U. Haemolysis of Plasmodium falciparum trophozoite-infected erythrocytes after artemisinin exposure. Br J Haematol. 1996 Feb;92(2):324–328. doi: 10.1046/j.1365-2141.1996.d01-1471.x. [DOI] [PubMed] [Google Scholar]
  77. Pittler M. H., Ernst E. Artemether for severe malaria: a meta-analysis of randomized clinical trials. Clin Infect Dis. 1999 Mar;28(3):597–601. doi: 10.1086/515148. [DOI] [PubMed] [Google Scholar]
  78. Price R. N., Nosten F., Luxemburger C., ter Kuile F. O., Paiphun L., Chongsuphajaisiddhi T., White N. J. Effects of artemisinin derivatives on malaria transmissibility. Lancet. 1996 Jun 15;347(9016):1654–1658. doi: 10.1016/s0140-6736(96)91488-9. [DOI] [PubMed] [Google Scholar]
  79. Pukrittayakamee S., Supanaranond W., Looareesuwan S., Vanijanonta S., White N. J. Quinine in severe falciparum malaria: evidence of declining efficacy in Thailand. Trans R Soc Trop Med Hyg. 1994 May-Jun;88(3):324–327. doi: 10.1016/0035-9203(94)90102-3. [DOI] [PubMed] [Google Scholar]
  80. Silamut Kamolrat, Newton Paul N., Teja-Isavadharm Paktiya, Suputtamongkol Yupin, Siriyanonda Duangsuda, Rasameesoraj Maneerat, Pukrittayakamee Sasithon, White Nicholas J. Artemether bioavailability after oral or intramuscular administration in uncomplicated falciparum malaria. Antimicrob Agents Chemother. 2003 Dec;47(12):3795–3798. doi: 10.1128/AAC.47.12.3795-3798.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Suputtamongkol Y., Newton P. N., Angus B., Teja-Isavadharm P., Keeratithakul D., Rasameesoraj M., Pukrittayakamee S., White N. J. A comparison of oral artesunate and artemether antimalarial bioactivities in acute falciparum malaria. Br J Clin Pharmacol. 2001 Dec;52(6):655–661. doi: 10.1046/j.1365-2125.2001.01458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Sutherland Colin J., Drakeley Christopher J., Obisike Uche, Coleman Rosalind, Jawara Musa, Targett Geoffrey A. T., Milligan Paul, Pinder Margaret, Walraven Gijs. The addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children delays, but does not prevent treatment failure. Am J Trop Med Hyg. 2003 Jul;69(1):19–25. [PubMed] [Google Scholar]
  83. Taylor T. E., Wills B. A., Kazembe P., Chisale M., Wirima J. J., Ratsma E. Y., Molyneux M. E. Rapid coma resolution with artemether in Malawian children with cerebral malaria. Lancet. 1993 Mar 13;341(8846):661–662. doi: 10.1016/0140-6736(93)90423-e. [DOI] [PubMed] [Google Scholar]
  84. Teja-Isavadharm P., Nosten F., Kyle D. E., Luxemburger C., Ter Kuile F., Peggins J. O., Brewer T. G., White N. J. Comparative bioavailability of oral, rectal, and intramuscular artemether in healthy subjects: use of simultaneous measurement by high performance liquid chromatography and bioassay. Br J Clin Pharmacol. 1996 Nov;42(5):599–604. doi: 10.1111/j.1365-2125.1996.tb00115.x. [DOI] [PubMed] [Google Scholar]
  85. Teja-Isavadharm P., Watt G., Eamsila C., Jongsakul K., Li Q., Keeratithakul G., Sirisopana N., Luesutthiviboon L., Brewer T. G., Kyle D. E. Comparative pharmacokinetics and effect kinetics of orally administered artesunate in healthy volunteers and patients with uncomplicated falciparum malaria. Am J Trop Med Hyg. 2001 Dec;65(6):717–721. doi: 10.4269/ajtmh.2001.65.717. [DOI] [PubMed] [Google Scholar]
  86. Teja-Isavadharm Paktiya, Peggins James O., Brewer Thomas G., White Nicholas J., Webster H. Kyle, Kyle Dennis E. Plasmodium falciparum-based bioassay for measurement of artemisinin derivatives in plasma or serum. Antimicrob Agents Chemother. 2004 Mar;48(3):954–960. doi: 10.1128/AAC.48.3.954-960.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Toovey Stephen, Jamieson Andrew. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether. Trans R Soc Trop Med Hyg. 2004 May;98(5):261–269. doi: 10.1016/j.trstmh.2003.11.001. [DOI] [PubMed] [Google Scholar]
  88. Tran T. H., Day N. P., Nguyen H. P., Nguyen T. H., Tran T. H., Pham P. L., Dinh X. S., Ly V. C., Ha V., Waller D. A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med. 1996 Jul 11;335(2):76–83. doi: 10.1056/NEJM199607113350202. [DOI] [PubMed] [Google Scholar]
  89. Udomsangpetch R., Pipitaporn B., Krishna S., Angus B., Pukrittayakamee S., Bates I., Suputtamongkol Y., Kyle D. E., White N. J. Antimalarial drugs reduce cytoadherence and rosetting Plasmodium falciparum. J Infect Dis. 1996 Mar;173(3):691–698. doi: 10.1093/infdis/173.3.691. [DOI] [PubMed] [Google Scholar]
  90. Utzinger J., N'Goran E. K., N'Dri A., Lengeler C., Xiao S., Tanner M. Oral artemether for prevention of Schistosoma mansoni infection: randomised controlled trial. Lancet. 2000 Apr 15;355(9212):1320–1325. doi: 10.1016/s0140-6736(00)02114-0. [DOI] [PubMed] [Google Scholar]
  91. Van Vugt M., Angus B. J., Price R. N., Mann C., Simpson J. A., Poletto C., Htoo S. E., Looareesuwan S., White N. J., Nosten F. A case-control auditory evaluation of patients treated with artemisinin derivatives for multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg. 2000 Jan;62(1):65–69. doi: 10.4269/ajtmh.2000.62.65. [DOI] [PubMed] [Google Scholar]
  92. Vennerstrom Jonathan L., Arbe-Barnes Sarah, Brun Reto, Charman Susan A., Chiu Francis C. K., Chollet Jacques, Dong Yuxiang, Dorn Arnulf, Hunziker Daniel, Matile Hugues. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature. 2004 Aug 19;430(7002):900–904. doi: 10.1038/nature02779. [DOI] [PubMed] [Google Scholar]
  93. Walker O., Salako L. A., Omokhodion S. I., Sowunmi A. An open randomized comparative study of intramuscular artemether and intravenous quinine in cerebral malaria in children. Trans R Soc Trop Med Hyg. 1993 Sep-Oct;87(5):564–566. doi: 10.1016/0035-9203(93)90092-5. [DOI] [PubMed] [Google Scholar]
  94. White N. J. Assessment of the pharmacodynamic properties of antimalarial drugs in vivo. Antimicrob Agents Chemother. 1997 Jul;41(7):1413–1422. doi: 10.1128/aac.41.7.1413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. White N. J. Clinical pharmacokinetics and pharmacodynamics of artemisinin and derivatives. Trans R Soc Trop Med Hyg. 1994 Jun;88 (Suppl 1):S41–S43. doi: 10.1016/0035-9203(94)90471-5. [DOI] [PubMed] [Google Scholar]
  96. White N. J., Krishna S. Treatment of malaria: some considerations and limitations of the current methods of assessment. Trans R Soc Trop Med Hyg. 1989 Nov-Dec;83(6):767–777. doi: 10.1016/0035-9203(89)90322-2. [DOI] [PubMed] [Google Scholar]
  97. White N. J., Nosten F., Looareesuwan S., Watkins W. M., Marsh K., Snow R. W., Kokwaro G., Ouma J., Hien T. T., Molyneux M. E. Averting a malaria disaster. Lancet. 1999 Jun 5;353(9168):1965–1967. doi: 10.1016/s0140-6736(98)07367-x. [DOI] [PubMed] [Google Scholar]
  98. White Nicholas J. Antimalarial drug resistance. J Clin Invest. 2004 Apr;113(8):1084–1092. doi: 10.1172/JCI21682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. White Nicholas J. Antimalarial drug resistance. J Clin Invest. 2004 Apr;113(8):1084–1092. doi: 10.1172/JCI21682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Xiao S. H., Booth M., Tanner M. The prophylactic effects of artemether against Schistosoma japonicum infections. Parasitol Today. 2000 Mar;16(3):122–126. doi: 10.1016/s0169-4758(99)01601-4. [DOI] [PubMed] [Google Scholar]
  101. ter Kuile F., White N. J., Holloway P., Pasvol G., Krishna S. Plasmodium falciparum: in vitro studies of the pharmacodynamic properties of drugs used for the treatment of severe malaria. Exp Parasitol. 1993 Feb;76(1):85–95. doi: 10.1006/expr.1993.1010. [DOI] [PubMed] [Google Scholar]
  102. van Agtmael M. A., Cheng-Qi S., Qing J. X., Mull R., van Boxtel C. J. Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria. Int J Antimicrob Agents. 1999 Jul;12(2):151–158. doi: 10.1016/s0924-8579(99)00063-1. [DOI] [PubMed] [Google Scholar]
  103. van Hensbroek M. B., Onyiorah E., Jaffar S., Schneider G., Palmer A., Frenkel J., Enwere G., Forck S., Nusmeijer A., Bennett S. A trial of artemether or quinine in children with cerebral malaria. N Engl J Med. 1996 Jul 11;335(2):69–75. doi: 10.1056/NEJM199607113350201. [DOI] [PubMed] [Google Scholar]
  104. van Vugt M., Looareesuwan S., Wilairatana P., McGready R., Villegas L., Gathmann I., Mull R., Brockman A., White N. J., Nosten F. Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria. Trans R Soc Trop Med Hyg. 2000 Sep-Oct;94(5):545–548. doi: 10.1016/s0035-9203(00)90082-8. [DOI] [PubMed] [Google Scholar]
  105. von Seidlein L., Milligan P., Pinder M., Bojang K., Anyalebechi C., Gosling R., Coleman R., Ude J. I., Sadiq A., Duraisingh M. Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial. Lancet. 2000 Jan 29;355(9201):352–357. doi: 10.1016/S0140-6736(99)10237-X. [DOI] [PubMed] [Google Scholar]
  106. von Seidlein Lorenz, Walraven Gijs, Milligan Paul J., Alexander Neal, Manneh Fandingding, Deen Jacqueline L., Coleman Roz, Jawara Musa, Lindsay Steve W., Drakeley Chris. The effect of mass administration of sulfadoxine-pyrimethamine combined with artesunate on malaria incidence: a double-blind, community-randomized, placebo-controlled trial in The Gambia. Trans R Soc Trop Med Hyg. 2003 Mar-Apr;97(2):217–225. doi: 10.1016/s0035-9203(03)90125-8. [DOI] [PubMed] [Google Scholar]

Articles from Postgraduate Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES