Severe embryotoxicity of artemisinin derivatives in experimental animals, but possibly safe in pregnant women

Molecules

Volumn 15, Issue 1, 2010, Pages 40-57

  Li, Qigui ^a   Weina, Peter J ^a  

^a WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

Author keywords

Artemisinins; Artesunate; Dihydroartemisinin; Embryotoxicity; Pharmacokinetics; Pregnant animals; Pregnant women

Indexed keywords

ARTEMISININ DERIVATIVE; TERATOGENIC AGENT;

ANIMAL; ANIMAL EMBRYO; DRUG EFFECT; DRUG TOXICITY; EXPERIMENTAL ANIMAL; FEMALE; HUMAN; PREGNANCY; PRENATAL DEVELOPMENT; REVIEW;

ANIMALS; ANIMALS, LABORATORY; ARTEMISININS; DRUG TOXICITY; EMBRYO, MAMMALIAN; FEMALE; HUMANS; PREGNANCY; TERATOGENS;

EID: 75749097693     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules15010040     Document Type: Review

References (63)

1. WHO. WHO Guidelines for the Treatment of Malaria; World Health Organization: Geneva, Switzerland, 2006; http://www.who.int/malaria/docs/ TreatmentGuidelines2006.pdf, accessed on December 24, 2009.
2. 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, 33, 2009-2016. (Pubitemid 33152395)
3. Adam, I.; Ali, D.M.; Abdalla, M.A. Artesunate plus sulfadoxine- pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria during pregnancy in eastern Sudan. Trans. R. Soc. Trop. Med. Hyg. 2006, 100, 632-635.
4. Dellicour, S.; Hall, S.; Chandramohan, D.; Greenwood, B. The safety of artemisinins during pregnancy: a pressing question. Malar. J. 2007, 6, 15. (Pubitemid 46321435)
5. WHO. Assessment of the safety of artemisinin compounds in pregnancy. In The Special Programme for Research and Training Diseases (TDR) and The Global Malaria Programme of the World Health Organization; World Health Organization: Geneva, Switzerland, 2006; http://www.who.int/malaria/publications/atoz/ 9789241596114/en/, accessed on December 24, 2009.
6. Efferth, T.; Dunstan, H.; Sauerbrey, A.; Miyachi, H.; Chitambar, C.R. The anti-malarial artesunate is also active against cancer. Int. J. Oncol. 2001, 18, 767-773.
7. Efferth, T. Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in cancer cells. Curr. Drug Targets 2006, 7, 407-421. (Pubitemid 43744832)
8. Chen, H.H.; Zhou, H.J.; Fang, X. Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro. Pharmacol. Res. 2003, 48, 231-236. (Pubitemid 36818928)
9. Chen, H.H.; Zhou, H.J.; Wu, G.D.; Lou, X.E. Inhibitory effects of artesunate on angiogenesis and on expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1. Pharmacology 2004, 71, 1-9.
10. Schmuck, G.; Klaus, A.M.; Krötlinger, F.; Langewische, F.W. Developmental and reproductive toxicity studies on artemisone. Birth. Defects Res. B Dev. Reprod. Toxicol. 2009, 86, 131-143.
11. Longo, M.; Zanoncelli, S.; Torre, P.D.; Rifiettuto, M.; Coceo, F.; Pesenti, M.; Giusti, A.; Colombo, P.; Brughera, M.; Mazué, G.; Navaratman, V.; Gomes, M.; Olliaro, P. In vivo and in vitro investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos. Reprod. Toxicol. 2006, 22, 797-810. (Pubitemid 44566455)
12. Longo, M.; Zanoncelli, S.; Manera, D.; Brughera, M.; Colombo, P.; Lansen, J.; Mazué, G.; Gomes, M.; Taylor, W.R.; Olliaro, P. Effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos in vitro. Reprod. Toxicol. 2006, 21, 83-93. (Pubitemid 43048778)
13. Longo, M.; Zanoncelli, S.; Torre P.D.; Rosa, F.; Giusti, A.; Colombo, P.; Brughera, M.; Mazué, G.; Olliaro, P. Investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). Reprod. Toxicol. 2008, 25, 433-441.
14. Chen, H.H.; Zhou, H.J.; Wang, W.Q.; Wu, G.D. Antimalarial dihydroartemisinin also inhibits angiogenesis. Cancer Chemother. Pharmacol. 2004, 53, 423-432.
15. White, T.E.; Bushdid, P.B.; Ritter, S.; Laffan, S.B.; Clark, R.L. Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity In vivo. Birth Defects Res. B Dev. Reprod. Toxicol. 2006, 77, 413-429.
16. Li, Q.; Si, Y.; Smith, K.S.; Zeng, Q.; Weina, P.J. Embryotoxicity of artesunate in animal species related to drug tissue distribution and toxicokinetic profiles. Birth Defects Res. B Dev. Reprod. Toxicol. 2008, 83, 435-445.
17. Li, Q.; Si, Y.Z.; Xie, L.H.; Zhang, J.; Weina, P. Severe embryolethality of artesunate related to pharmacokinetics following intravenous and intramuscular doses in pregnant rats. Birth Defects Res. B Dev. Reprod. Toxicol. 2009, 86, 385-393.
18. White, T.E.; Clark, R.L. Sensitive periods for developmental toxicity of orally administered artesunate in the rat. Birth Defects Res. B Dev. Reprod. Toxicol. 2008, 83, 407-417.
19. Clark, R.L.; Arima, A.; Makori, N.; Nakata, Y.; Bernard, F.; Gristwood, W.; Harrell, A.; White, T.E.; Wier, P.J. Artesunate: developmental toxicity and toxicokinetics in monkeys. Birth Defects Res. B Dev. Reprod Toxicol. 2008, 83, 418-434.
20. Lensch, M.W.; Daley, G.Q. Origins of mammalian hematopoiesis: In vivo paradigms and in vitro models. Curr. Top. Dev. Biol. 2004, 60, 127-196.
21. Segel, G.; Palis, J. Hematology of the Newborn. In Williams Hematology; Beutler, E., Lichtman, M., Coller, B., Kipps, T., Seligsohn, U., ed.; McGraw-Hill: New York, NY, USA, 2001; p. 77.
22. Kelemen, E.; Calvo, W.; Fliedner, T. Atlas of Human Hemopoietic Development; Springer-Verlag: Berlin, Germany, 1979; p. 21.
23. Dawes, M.; Chowienczyk, P.J. Drugs in pregnancy. Pharmacokinetics in pregnancy. Best Pract. Res. Clin. Obstet. Gynaecol. 2001, 15, 819-826.
24. Nosten, F.; McGready, R.; d'Alessandro, U.; Bonell, A.; Verhoeff, F.; Menendez, C.; Mutabingwa, T.; Brabin, B. Antimalarial Drugs in Pregnancy: a review. Currt. Drug Saf 2006, 1, 1-15.
25. Akintonwa, A.; Meyer, M.C.; Yau, M.K. Placental transfer of chloroquine in pregnant rabbits. Res. Commun. Chem. Pathol. Pharmacol. 1983, 40, 443-455.
26. 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, 44, 972-977.
27. Menendez, C. Malaria during pregnancy. Curr. Mol. Med. 2006, 6, 269-273.
28. Clark, R.L. Embryotoxicity of the artemisinin antimalarials and potential consequences for use in women in the first trimester. Reprod. Toxicol. 2009, 28, 285-296.
29. D'Alessandro, S.; Gelati, M.; Basilico, N.; Parati, EA.; Haynes, R.K.; Taramelli, D. Differential effects on angiogenesis of two antimalarial compounds, dihydroartemisinin and artemisone: implications for embryotoxicity. Toxicology 2007, 241, 66-74. (Pubitemid 47599780)
30. Fakeye, T.O.; Fehintola, F.A.; Ademowo, O.G.; Walker, O. Therapeutic monitoring of chloroquine in pregnant women with malaria. West Afr. J. Med. 2002, 21, 286-287.
31. Massele, A.Y.; Kilewo, C.; Aden Abdi, Y.; Tomson, G.; Diwan, V.K.; Ericsson, O.; Rimoy, G.; Gustafsson, L.L. Chloroquine blood concentrations and malaria prophylaxis in Tanzanian women during the second and third trimesters of pregnancy. Eur. J. Clin. Pharmacol. 1997, 52, 299-305.
32. Na Bangchang, K.; Davis, T.M.; Looareesuwan, S.; White, N.J.; Bunnag, D.; Karbwang, J. Mefloquine pharmacokinetics in pregnant women with acute falciparum malaria. Trans. R. Soc. Trop. Med. Hyg. 1994, 88, 321-323. (Pubitemid 24206457)
33. McGready, R.; Stepniewska, K.; Seaton, E.; Cho, T.; Cho, D.; Ginsberg, A.; Edstein, M.D.; Ashley, E.; Looareesuwan, S.; White, N.J.; Nosten, F. Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil. Eur. J. Clin. Pharmacol. 2003, 59, 553-557.
34. Na-Bangchang, K.; Manyando, C.; Ruengweerayut, R.; Kioy, D.; Mulenga, M.; Miller, G.B.; Konsil, J. The pharmacokinetics and pharmacodynamics of atovaquone and proguanil for the treatment of uncomplicated falciparum malaria in third - trimester pregnant women. Eur. J. Clin. Pharmacol. 2005, 61, 573-582. (Pubitemid 41414241)
35. McGready, R.; Stepniewska, K.; Edstein, M.D.; Cho, T.; Gilveray, G.; Looareesuwan, S.; White, N.J.; Nosten, F. The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. Eur. J. Clin. Pharmacol. 2003, 59, 545-552. (Pubitemid 37368905)
36. McGready, R.; Stepniewska, K.; Ward, S. A.; Cho, T.; Gilveray, G.; Looareesuwan, S.; White, N.J.; Nosten, F. Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria. Eur. J. Clin. Pharmacol. 2006, 62, 367-371.
37. Ward, S. A.; Sevene, E.J.; Hastings, I.M.; Nosten, F.; McGready, R. Antimalarial drugs and pregnancy: safety, pharmacokinetics, and pharmacovigilance. Lancet Infect. Dis. 2007, 7, 136-144. (Pubitemid 46123134)
38. Clark, R.L.; White, T.E.; Clode, S.A.; Gaunt, I.; Winstanley, P.; Ward, S.A. Developmental toxicity of artesunate and an artesunate combination in the rat and rabbit. Birth Defects Res. B Dev. Reprod. Toxicol. 2004, 71, 380-394.
39. Wang, T.Y. Follow-up observation on the therapeutic effects and remote reactions of artemisinin (Qinghaosu) and artemether in treating malaria in pregnant woman. J. Tradit. Chin. Med. 1989, 9, 28-30.
40. Guo, X.B.; Fu, L.C.; Fan, T.T.; Cai, D.F.; Li, G.Q. Clinical Trials on Qinghaosu and Its Derivatives; Li, G.-Q., Guo, X.B., Fu, Y., eds.; Guangzhou College of Traditional Chinese Medicine: Guangzhou, China, 1999; pp. 39-42, 59-63.
41. 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, 88 (Suppl. 1), S5-S6. (Pubitemid 24206475)
42. Sowunmi, A.; Oduola, A.M.; Ogundahunsi, O.A.; Fehintola, F.A.; Ilesanmi, O.A.; Akinyinka, O.O.; Arowojolu, A.O. Randomised trial of artemether versus artemether and mefloquine for the treatment of chloroquine/sufadoxine- pyrimethamine-resistant falciparum malaria during pregnancy. J. Obstet. Gynaecol. 1998, 18, 322-327.
43. McGready, R.; Cho, T.; Cho, J.J.; Simpson, J.A.; Luxemburger, C.; Dubowitz, L.; Looareesuwan, S.; White, N.J.; Nosten, F. Artemisinin derivatives in the treatment of falciparum malaria in pregnancy. Trans. R. Soc. Trop. Med. Hyg. 1998, 92, 430-433. (Pubitemid 28409894)
44. McGready, R.; Cho, T.; Samuel; Villegas, L.; Brockman, A.; van Vugt, M.; Looareesuwan, S.; White, N.J.; Nosten, F. Randomized comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy. Trans. R. Soc. Trop. Med. Hyg. 2001, 95, 651-656. (Pubitemid 34202258)
45. Adam, I.; Elwasila, E.; Mohammed, Ali D.A.; Elansari, E.; Elbashir, M.I. Artemether in the treatment of falciparum malaria during pregnancy in eastern Sudan. Trans. R. Soc. Trop. Med. Hyg. 2004, 98, 509-513.
46. McGready, R.; Tan, S.O.; Ashley, E.A.; Pimanpanarak, M.; Viladpai-Nguen, J.; Phaiphun, L.; Wüstefeld, K.; Barends, M.; Laochan, N.; Keereecharoen, L.; Lindegardh, N.; Singhasivanon, P.; White, N.J.; Nosten, F. A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated Plasmodium falciparum treatment in pregnancy. PLoS Med. 2008, 5, e253.
47. Adam, I.; Elhassan, E.M.; Omer, E.M.; Abdulla, M.A.; Mahgoub, H.M.; Adam, G.K. Safety of artemisinins during early pregnancy, assessed in 62 Sudanese women. Ann. Trop. Med. Parasitol. 2009, 103, 205-210.
48. McGready, R.; Brockman, A.; Cho, T.; Cho, D.; van Vugt, M.; Luxemburger, C.; Chongsuphajaisiddhi, T.; White, N.J.; Nosten, F. Randomized comparison of mefioquineartesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy. Trans. R. Soc. Trop. Med. Hyg. 2000, 94, 689-693.
49. Bounyasong, S. Randomized trial of artesunate and mefloquine in comparison with quinine sulfate to treat P. falciparum malaria pregnant women. J. Med. Assoc. Thai. 2001, 84, 1289-1299. (Pubitemid 34136423)
50. 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, 95, 424-428.
51. McGready, R.; Keo, N.K.; Villegas, L.; White, N.J.; Looareesuwan, S.; Nosten, F. Artesunateatovaquone-proguanil rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a preliminary report. Trans. R. Soc. Trop. Med. Hyg. 2003, 97, 592-594. (Pubitemid 40590101)
52. McGready, R.; Ashley, E.A.; Moo, E.; Cho, T.; Barends, M.; Hutagalung, R.; Looareesuwan, S.; White, N.J.; Nosten, F. A randomized comparison of artesunate-atovaquone-proguanil versus quinine in treatment for uncomplicated falciparum malaria during pregnancy. J. Infect. Dis. 2005, 192, 846-853. (Pubitemid 41193082)
53. Kalilani, L.; Mofolo, I.; Chaponda, M.; Rogerson, S.J.; Alker, A.P.; Kwiek, J.J.; Meshnick, S.R. A randomized controlled pilot trial of azithromycin or artesunate added to sulfadoxinepyrimethamine as treatment for malaria in pregnant women. PLoS One 2007, 2, e1166.
54. Kaye, D.K.; Nshemerirwe, R.; Mutyaba, T.S.; Ndeezi, G. A randomized clinical trial comparing safety, clinical and parasitological response to artemether-lumefantrine and chlorproguanildapsone in treatment of uncomplicated malaria in pregnancy in Mulago hospital, Uganda. J. Infect. Dev. Ctries. 2008, 2, 135-139.
55. Rijken, M.J.; McGready, R.; Boel, M.E.; Barends, M.; Proux, S.; Pimanpanarak, M.; Singhasivanon, P.; Nosten, F. Dihydroartemisinin-piperaquine rescue treatment of multidrugresistant Plasmodium falciparum malaria in pregnancy: a preliminary report. Am. J. Trop. Med. Hyg. 2008, 78, 543-545. (Pubitemid 351845153)
56. Mutabingwa, T.K.; Muze, K.; Ord, R.; Briceño, M.; Greenwood, B.M.; Drakeley, C.; Whitty, C.J. Randomized trial of artesunate-amodiaquine, sulfadoxine-pyrimethamine+amodiaquine, chlorproguanal-dapsone and SP for malaria in pregnancy in Tanzania. PLoS One 2009, 4, e5138.
57. Orton, L.; Garner, P. Drugs for treating uncomplicated malaria in pregnant women. Cochrane Database Syst. Rev. 2005, 20, CD004912.
58. Geyer, H.J.; Scheuntert, I.; Rapp, K.; Kettrup, A.; Körte, F.; Greim, H.; Rozman, K. Correlation between acute toxicity of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and total body fat content in mammals. Toxicology 1990, 65, 97-107.
59. Kimbrough, R.D. How toxic is 2,3,7,8-tetrachlorodibenzodioxin to humans? J. Toxicol. Environ. Health. 1990, 30, 261-271.
60. Culotta, E.; Koshland, D.E., Jr. DNA repair works it works its way to the top. Science 1994, 266, 1926-1929.
61. Steketee, R.W.; Wirima, J.J.; Campbell, C.C. Developing effective strategies for malaria prevention programs for pregnant African women. Am. J. Trop. Med. Hyg. 1996, 55 (Suppl. 1), 95-100. (Pubitemid 26268585)
62. Steketee, R.W.; Nahlen, BX.; Parise, M.E.; Menendez, C. The burden of malaria in pregnancy in malaria-endemic areas. Am. J. Trop. Med. Hyg. 2001, 64 (Suppl. 1-2), 28-35. (Pubitemid 32552569)
63. Newman, R.D.; Parise, M.E.; Slutsker, L.; Náhlen, B.; Steketee, R.W. Safety, efficacy and determinants of effectiveness of antimalarial drugs during pregnancy: implications for prevention programmes in Plasmodium falciparum-endemic sub-Saharan Africa. Trop. Med. Int. Health. 2003, 8, 488-506. (Pubitemid 36724013)