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Malaria Journal
Published in: Malaria Journal 1/2014

Open Access 01-12-2014 | Research

Fixed dose artesunate amodiaquine – a phase IIb, randomized comparative trial with non-fixed artesunate amodiaquine

Authors: Bernhards Ogutu, Elizabeth Juma, Charles Obonyo, Vincent Jullien, Gwenaelle Carn, Michel Vaillant, Walter Robert John Taylor, Jean-René Kiechel

Published in: Malaria Journal | Issue 1/2014

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Abstract

Background

Pharmacokinetic (PK) and pharmacodynamic (PD) data are limited for artesunate (AS) and amodiaquine (AQ) in uncomplicated Plasmodium falciparum.

Methods

From 2007-8, 54 P. falciparum-infected, Kenyan adults were assigned randomly fixed dose (FD) ASAQ (n = 26) or non-fixed (NF) ASAQ (n = 28). Total doses were 600 mg AS (both arms) + 1,620 mg (FD) or 1,836 mg (NF)AQ. Follow-up extended over 28 days. PK data were collected for AS, dihydroartemisinin (DHA), AS + DHA combined as DHA equivalents (DHAeq), AQ, desethylamodiaquine (DAQ),and their relationships assessed against the PD collected data consisting of parasitological efficacy, adverse events (AEs), and the Bazett’s corrected QTinterval (QTcB).

Results

Mean AUC 0-72 of dihydroartemisinin equivalents (DHAeq) when administered as a fixed dose (FD) compared to NF dose were similar: 24.2 ±4.6 vs 26.4±6.9 µmol*h/L (p = 0.68) Parasite clearance rates were also similar after 24 hrs: 17/25 (68%) vs 18/28(64.3%) (p = 0.86),as well as at 48 hrs: 25/8 (100%)vs 26 (92.9%)/28 (p = 0.49). Mean FD vs NF DAQ AUC0-28 were 27.6±3.19 vs 32.7±5.53 mg*h/L (p = 0.0005). Two PCR-proven new infections occurred on Day (D) 28 for estimated, in vivo, DAQ minimum inhibitory concentrations of 15.2 and 27.5 ng/mL. Combining the FD and NF arms, the mean QTcB at D2+4 hrs increased significantly (p = 0.0059) vs baseline: 420 vs 410 ms (∆ = 9.02 (95% confidence interval 2.72-15.31 ms), explained by falling heart rates, increasing DAQ concentrations and female sex in a general linear mixed effects model. Ten of 108 (9.26%) AEs (5/arm) reported by 37/54 (68.5%) patients were possibly or probably drug related. Severe, asymptomatic neutropaenia developed in 2/47 (4.25%) patients on D28: 574/µL (vs D0: 5,075/µL), and 777/µL (vs D0: 3,778/µL).

Conclusions

Tolerability of both formulations was good. For QTcB, a parameter for ECG modifications, increases were modest and due to rising DAQ concentrations and falling heart rates as malaria resolved. Rapid parasite clearance rates and no resistant infections suggest effective pharmacokinetics of both formulations.
Appendix
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Literature
1.
Kiechel JR, Pecoul B: ASAQ, a breakthrough in the fight against malaria. Med Trop (Mars). 2007, 67: 109-110.
2.
Bompart F, Kiechel JR, Sebbag R, Pecoul B: Innovative public-private partnerships to maximize the delivery of anti-malarial medicines: lessons learned from the ASAQ Winthrop experience. Malar J. 2011, 10: 143-10.1186/1475-2875-10-143.PubMedCentralCrossRefPubMed
3.
Taylor WR, Terlouw DJ, Olliaro PL, White NJ, Brasseur P, ter Kuile FO: Use of weight-for-age-data to optimize tablet strength and dosing regimens for a new fixed-dose artesunate-amodiaquine combination for treating falciparum malaria. Bull World Health Organ. 2006, 84: 956-964. 10.2471/BLT.06.031492.PubMedCentralCrossRefPubMed
4.
Brasseur P, Agnamey P, Gaye O, Cisse M, Badiane M, Vaillant M, Taylor WR, Olliaro P: Dosing accuracy of artesunate and amodiaquine as treatment for falciparum malaria in Casamance, Senegal. Trop Med Int Health. 2009, 14: 79-87.CrossRefPubMed
5.
Faucher JF, Aubouy A, Adeothy A, Cottrell G, Doritchamou J, Gourmel B, Houze P, Kossou H, Amedome H, Massougbodji A, Cot M, Deloron P: Comparison of sulfadoxine-pyrimethamine, unsupervised artemether-lumefantrine, and unsupervised artesunate-amodiaquine fixed-dose formulation for uncomplicated Plasmodium falciparum malaria in Benin: a randomized effectiveness noninferiority trial. J Infect Dis. 2009, 200: 57-65. 10.1086/599378.CrossRefPubMed
6.
Sirima SB, Tiono AB, Gansane A, Diarra A, Ouedraogo A, Konate AT, Kiechel JR, Morgan CC, Olliaro PL, Taylor WR: The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum. Malar J. 2009, 8: 48-10.1186/1475-2875-8-48.PubMedCentralCrossRefPubMed
7.
Faye B, Kuete T, Kiki-Barro CP, Tine RC, Nkoa T, Ndiaye JL, Kakpo CA, Sylla K, El Menan H, Gaye O, Faye O, Same-Ekobo A, Moussa K: Multicentre study evaluating the non-inferiority of the new paediatric formulation of artesunate/amodiaquine versus artemether/lumefantrine for the management of uncomplicated Plasmodium falciparum malaria in children in Cameroon, Ivory Coast and Senegal. Malar J. 2012, 11: 433-10.1186/1475-2875-11-433.PubMedCentralCrossRefPubMed
8.
Espie E, Lima A, Atua B, Dhorda M, Flevaud L, Sompwe EM, Palma Urrutia PP, Guerin PJ: Efficacy of fixed-dose combination artesunate-amodiaquine versus artemether-lumefantrine for uncomplicated childhood Plasmodium falciparum malaria in Democratic Republic of Congo: a randomized non-inferiority trial. Malar J. 2012, 11: 174-10.1186/1475-2875-11-174.PubMedCentralCrossRefPubMed
9.
Gbotosho GO, Sowunmi A, Okuboyejo TM, Happi CT, Folarin OA, Michael OS, Adewoye EO: Therapeutic efficacy and effects of artemether-lumefantrine and artesunate-amodiaquine coformulated or copackaged on malaria-associated anemia in children with uncomplicated Plasmodium falciparum malaria in Southwest Nigeria. Am J Trop Med Hyg. 2011, 84: 813-819. 10.4269/ajtmh.2011.10-0582.PubMedCentralCrossRefPubMed
10.
Djalle D, Njuimo SP, Manirakiza A, Laganier R, Le Faou A, Rogier C: Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial. Malar J. 2014, 13: 9-10.1186/1475-2875-13-9.PubMedCentralCrossRefPubMed
11.
Ndiaye JL, Randrianarivelojosia M, Sagara I, Brasseur P, Ndiaye I, Faye B, Randrianasolo L, Ratsimbasoa A, Forlemu D, Moor VA, Traore A, Dicko Y, Dara N, Lameyre V, Diallo M, Djimde A, Same-Ekobo A, Gaye O: Randomized, multicentre assessment of the efficacy and safety of ASAQ–a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria. Malar J. 2009, 8: 125-10.1186/1475-2875-8-125.PubMedCentralCrossRefPubMed
12.
Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Greenhouse B, Staedke SG, Kamya MR, Dorsey G, Rosenthal PJ: Incidence of malaria and efficacy of combination antimalarial therapies over 4 years in an urban cohort of Ugandan children. PLoS One. 2010, 5: e11759-10.1371/journal.pone.0011759.PubMedCentralCrossRefPubMed
13.
Bonnet M, Roper C, Felix M, Coulibaly L, Kankolongo GM, Guthmann JP: Efficacy of antimalarial treatment in Guinea: in vivo study of two artemisinin combination therapies in Dabola and molecular markers of resistance to sulphadoxine-pyrimethamine in N'Zerekore. Malar J. 2007, 6: 54-10.1186/1475-2875-6-54.PubMedCentralCrossRefPubMed
14.
van den Broek I, Kitz C, Al Attas S, Libama F, Balasegaram M, Guthmann JP: Efficacy of three artemisinin combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in the Republic of Congo. Malar J. 2006, 5: 113-10.1186/1475-2875-5-113.PubMedCentralCrossRefPubMed
15.
Guthmann JP, Cohuet S, Rigutto C, Fortes F, Saraiva N, Kiguli J, Kyomuhendo J, Francis M, Noel F, Mulemba M, Balkan S: High efficacy of two artemisinin-based combinations (artesunate + amodiaquine and artemether + lumefantrine) in Caala, Central Angola. Am J Trop Med Hyg. 2006, 75: 143-145.PubMed
16.
Ibrahium AM, Kheir MM, Osman ME, Khalil IF, Alifrangis M, Elmardi KA, Malik EM, Adam I: Efficacies of artesunate plus either sulfadoxine-pyrimethamine or amodiaquine, for the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan. Ann Trop Med Parasitol. 2007, 101: 15-21. 10.1179/136485907X156924.CrossRefPubMed
17.
Ajayi IO, Browne EN, Bateganya F, Yar D, Happi C, Falade CO, Gbotosho GO, Yusuf B, Boateng S, Mugittu K, Cousens S, Nanyunja M, Pagnoni F: Effectiveness of artemisinin-based combination therapy used in the context of home management of malaria: a report from three study sites in sub-Saharan Africa. Malar J. 2008, 7: 190-10.1186/1475-2875-7-190.PubMedCentralCrossRefPubMed
18.
Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Bjorkman A: Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis. 2005, 41: 1079-1086. 10.1086/444460.CrossRefPubMed
19.
Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WR: Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial. Lancet. 2002, 359: 1365-1372. 10.1016/S0140-6736(02)08348-4.CrossRefPubMed
20.
Holmgren G, Hamrin J, Svard J, Martensson A, Gil JP, Bjorkman A: Selection of pfmdr1 mutations after amodiaquine monotherapy and amodiaquine plus artemisinin combination therapy in East Africa. Infect Genet Evol. 2007, 7: 562-569. 10.1016/j.meegid.2007.03.005.CrossRefPubMed
21.
Kabanywanyi AM, Mwita A, Sumari D, Mandike R, Mugittu K, Abdulla S: Efficacy and safety of artemisinin-based antimalarial in the treatment of uncomplicated malaria in children in southern Tanzania. Malar J. 2007, 6: 146-10.1186/1475-2875-6-146.PubMedCentralCrossRefPubMed
22.
Hamour S, Melaku Y, Keus K, Wambugu J, Atkin S, Montgomery J, Ford N, Hook C, Checchi F: Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations. Trans R Soc Trop Med Hyg. 2005, 99: 548-554. 10.1016/j.trstmh.2004.10.003.CrossRefPubMed
23.
Abacassamo F, Enosse S, Aponte JJ, Gomez-Olive FX, Quinto L, Mabunda S, Barreto A, Magnussen P, Ronn AM, Thompson R, Alonso PL: Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria. Trop Med Int Health. 2004, 9: 200-208. 10.1046/j.1365-3156.2003.01182.x.CrossRefPubMed
24.
Ndounga M, Mayengue PI, Casimiro PN, Loumouamou D, Basco LK, Ntoumi F, Brasseur P: Artesunate-amodiaquine efficacy in Congolese children with acute uncomplicated falciparum malaria in Brazzaville. Malar J. 2013, 12: 53-10.1186/1475-2875-12-53.PubMedCentralCrossRefPubMed
25.
Swarthout TD, van den Broek IV, Kayembe G, Montgomery J, Pota H, Roper C: Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes. Trop Med Int Health. 2006, 11: 1503-1511. 10.1111/j.1365-3156.2006.01710.x.CrossRefPubMed
26.
Rwagacondo CE, Karema C, Mugisha V, Erhart A, Dujardin JC, Van Overmeir C, Ringwald P, D'Alessandro U: Is amodiaquine failing in Rwanda? Efficacy of amodiaquine alone and combined with artesunate in children with uncomplicated malaria. Trop Med Int Health. 2004, 9: 1091-1098. 10.1111/j.1365-3156.2004.01316.x.CrossRefPubMed
27.
Bonnet M, Broek I, van Herp M, Urrutia PP, van Overmeir C, Kyomuhendo J, Ndosimao CN, Ashley E, Guthmann JP: Varying efficacy of artesunate+amodiaquine and artesunate+sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in the Democratic Republic of Congo: a report of two in-vivo studies. Malar J. 2009, 8: 192-10.1186/1475-2875-8-192.PubMedCentralCrossRefPubMed
28.
Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, Greenwood BM, Whitty CJ: Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet. 2005, 365: 1474-1480. 10.1016/S0140-6736(05)66417-3.CrossRefPubMed
29.
Grandesso F, Hagerman A, Kamara S, Lam E, Checchi F, Balkan S, Scollo G, Durand R, Guthmann JP: Low efficacy of the combination artesunate plus amodiaquine for uncomplicated falciparum malaria among children under 5 years in Kailahun, Sierra Leone. Trop Med Int Health. 2006, 11: 1017-1021. 10.1111/j.1365-3156.2006.01655.x.CrossRefPubMed
30.
Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, Badoe EV, Lamptey R, Goka BQ: Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up. Malar J. 2008, 7: 127-10.1186/1475-2875-7-127.PubMedCentralCrossRefPubMed
31.
Falade CO, Ogundele AO, Yusuf BO, Ademowo OG, Ladipo SM: High efficacy of two artemisinin-based combinations (artemether-lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria. Trop Med Int Health. 2008, 13: 635-643. 10.1111/j.1365-3156.2008.02043.x.CrossRefPubMed
32.
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, Pinoges L, Sundaygar T, Zolia YM, Jones JJ, Comte E, Bruneel A, Branger M, Jullien V, Carn G, Kiechel JR, Ashley EA, Guérin PJ: Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County Liberia. Malar J. 2013, 12: 250-10.1186/1475-2875-12-250.PubMedCentralCrossRefPubMed
33.
Neftel KA, Woodtly W, Schmid M, Frick PG, Fehr J: Amodiaquine induced agranulocytosis and liver damage. Br Med J (Clin Res Ed). 1986, 292: 721-723. 10.1136/bmj.292.6522.721.CrossRef
34.
Orrell C, Taylor WR, Olliaro P: Acute asymptomatic hepatitis in a healthy normal volunteer exposed to 2 oral doses of amodiaquine and artesunate. Trans R Soc Trop Med Hyg. 2001, 95: 517-518. 10.1016/S0035-9203(01)90024-0.CrossRefPubMed
35.
Markham LN, Giostra E, Hadengue A, Rossier M, Rebsamen M, Desmeules J: Emergency liver transplantation in amodiaquine-induced fulminant hepatitis. Am J Trop Med Hyg. 2007, 77: 14-15.PubMed
36.
Ngouesse B, Basco LK, Ringwald P, Keundjian A, Blackett KN: Cardiac effects of amodiaquine and sulfadoxine-pyrimethamine in malaria-infected African patients. Am J Trop Med Hyg. 2001, 65: 711-716.PubMed
37.
Adjei GO, Oduro-Boatey C, Rodrigues OP, Hoegberg LC, Alifrangis M, Kurtzhals JA, Goka BQ: Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine. Malar J. 2012, 11: 420-10.1186/1475-2875-11-420.PubMedCentralCrossRefPubMed
38.
White NJ, Looareesuwan S, Edwards G, Phillips RE, Karbwang J, Nicholl DD, Bunch C, Warrell DA: Pharmacokinetics of intravenous amodiaquine. Br J Clin Pharmacol. 1987, 23: 127-135. 10.1111/j.1365-2125.1987.tb03020.x.PubMedCentralCrossRefPubMed
39.
Stepniewska K, Taylor W, Sirima SB, Ouedraogo EB, Ouedraogo A, Gansane A, Simpson JA, Morgan CC, White NJ, Kiechel JR: Population pharmacokinetics of artesunate and amodiaquine in African children. Malar J. 2009, 8: 200-10.1186/1475-2875-8-200.PubMedCentralCrossRefPubMed
40.
Obonyo CO, Ochieng F, Taylor WR, Ochola SA, Mugitu K, Olliaro P, ter Kuile F, Oloo AJ: Artesunate plus sulfadoxine-pyrimethamine for uncomplicated malaria in Kenyan children: a randomized, double-blind, placebo-controlled trial. Trans R Soc Trop Med Hyg. 2003, 97: 585-591. 10.1016/S0035-9203(03)80038-X.CrossRefPubMed
41.
Holmgren G, Bjorkman A, Gil JP: Amodiaquine resistance is not related to rare findings of pfmdr1 gene amplifications in Kenya. Trop Med Int Health. 2006, 11: 1808-1812. 10.1111/j.1365-3156.2006.01742.x.CrossRefPubMed
42.
Zucker JR, Ruebush TK, Obonyo C, Otieno J, Campbell CC: The mortality consequences of the continued use of chloroquine in Africa: experience in Siaya, western Kenya. Am J Trop Med Hyg. 2003, 68: 386-390.PubMed
43.
Obonyo CO, Vulule J, Akhwale WS, Grobbee DE: In-hospital morbidity and mortality due to severe malarial anemia in western Kenya. Am J Trop Med Hyg. 2007, 77: 23-28.PubMed
44.
Thwing JI, Odero CO, Odhiambo FO, Otieno KO, Kariuki S, Ord R, Roper C, McMorrow M, Vulule J, Slutsker L, Newman RD, Hamel MJ, Desai M: In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya. Trop Med Int Health. 2009, 14: 294-300. 10.1111/j.1365-3156.2009.02222.x.CrossRefPubMed
45.
Snounou G, Beck HP: The use of PCR genotyping in the assessment of recrudescence or reinfection after antimalarial drug treatment. Parasitol Today. 1998, 14: 462-467. 10.1016/S0169-4758(98)01340-4.CrossRefPubMed
46.
WHO: Guidelines for the Treatment of Malaria. 2006, Geneva, Switzerland: World Health Organization
47.
Edwards IR, Aronson JK: Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000, 356: 1255-1259. 10.1016/S0140-6736(00)02799-9.CrossRefPubMed
48.
Krudsood S, Looareesuwan S, Tangpukdee N, Wilairatana P, Phumratanaprapin W, Leowattana W, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel JR, Taylor WR: New fixed-dose artesunate-mefloquine formulation against multidrug-resistant Plasmodium falciparum in adults: a comparative phase IIb safety and pharmacokinetic study with standard-dose nonfixed artesunate plus mefloquine. Antimicrob Agents Chemother. 2010, 54: 3730-3737. 10.1128/AAC.01187-09.PubMedCentralCrossRefPubMed
49.
Krudsood S, Looareesuwan S, Wilairatama P, Leowattana W, Tangpukdee N, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel JR, Taylor WR: Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand. Trop Med Int Health. 2011, 16: 458-465. 10.1111/j.1365-3156.2010.02714.x.CrossRefPubMed
50.
Jullien V, Ogutu B, Juma E, Carn G, Obonyo C, Kiechel JR: Population pharmacokinetics and pharmacodynamic considerations of amodiaquine and desethylamodiaquine in Kenyan adults with uncomplicated malaria receiving artesunate-amodiaquine combination therapy. Antimicrob Agents Chemother. 2010, 54: 2611-2617. 10.1128/AAC.01496-09.PubMedCentralCrossRefPubMed
51.
Price RN, Nosten F, White NJ: Prolongation of the QTc interval in African children treated for falciparum malaria. Am J Trop Med Hyg. 1998, 59: 503-PubMed
52.
Zwang J, Ndiaye JL, Djimde A, Dorsey G, Martensson A, Karema C, Olliaro P: Comparing changes in haematologic parameters occurring in patients included in randomized controlled trials of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa. Malar J. 2012, 11: 25-10.1186/1475-2875-11-25.PubMedCentralCrossRefPubMed
53.
Gupta RK, Van Vugt M, Paiphun L, Slight T, Looareesuwan S, White NJ, Nosten F: Short report: no evidence of cardiotoxicity of atovaquone-proguanil alone or in combination with artesunate. Am J Trop Med Hyg. 2005, 73: 267-268.PubMed
54.
Mytton OT, Ashley EA, Peto L, Price RN, La Y, Hae R, Singhasivanon P, White NJ, Nosten F: Electrocardiographic safety evaluation of dihydroartemisinin piperaquine in the treatment of uncomplicated falciparum malaria. Am J Trop Med Hyg. 2007, 77: 447-450.PubMed
55.
Karunajeewa H, Lim C, Hung TY, Ilett KF, Denis MB, Socheat D, Davis TM: Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin) in Cambodian children and adults with malaria. Br J Clin Pharmacol. 2004, 57: 93-99.PubMedCentralCrossRefPubMed
56.
van Vugt M, Ezzet F, Nosten F, Gathmann I, Wilairatana P, Looareesuwan S, White NJ: No evidence of cardiotoxicity during antimalarial treatment with artemether-lumefantrine. Am J Trop Med Hyg. 1999, 61: 964-967.PubMed
57.
Hietala SF, Bhattarai A, Msellem M, Roshammar D, Ali AS, Stromberg J, Hombhanje FW, Kaneko A, Bjorkman A, Ashton M: Population pharmacokinetics of amodiaquine and desethylamodiaquine in pediatric patients with uncomplicated falciparum malaria. J Pharmacokinet Pharmacodyn. 2007, 34: 669-686. 10.1007/s10928-007-9064-2.CrossRefPubMed
58.
Orrell C, Little F, Smith P, Folb P, Taylor W, Olliaro P, Barnes KI: Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers. Eur J Clin Pharmacol. 2008, 64: 683-690. 10.1007/s00228-007-0452-8.PubMedCentralCrossRefPubMed
59.
Navaratnam V, Ramanathan S, Wahab MS, Siew Hua G, Mansor SM, Kiechel JR, Vaillant M, Taylor WR, Olliaro P: Tolerability and pharmacokinetics of non-fixed and fixed combinations of artesunate and amodiaquine in Malaysian healthy normal volunteers. Eur J Clin Pharmacol. 2009, 65: 809-821. 10.1007/s00228-009-0656-1.PubMedCentralCrossRefPubMed
60.
Aubouy A, Mayombo J, Keundjian A, Bakary M, Le Bras J, Deloron P: Lack of prediction of amodiaquine efficacy in treating Plasmodium falciparum malaria by in vitro tests. Am J Trop Med Hyg. 2004, 71: 294-296.PubMed
Metadata
Title
Fixed dose artesunate amodiaquine – a phase IIb, randomized comparative trial with non-fixed artesunate amodiaquine
Authors
Bernhards Ogutu
Elizabeth Juma
Charles Obonyo
Vincent Jullien
Gwenaelle Carn
Michel Vaillant
Walter Robert John Taylor
Jean-René Kiechel
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2014
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-13-498

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Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

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Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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