A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand

被引:136
作者
Lefèvre, G
Looareesuwan, S
Treeprasertsuk, S
Krudsood, S
Silachamroon, U
Gathmann, I
Mull, R
Bakshi, R
机构
[1] Mahidol Univ, Fac Trop Med, Bangkok, Thailand
[2] Novartis Pharma AG, Int Clin Dev, CH-4002 Basel, Switzerland
关键词
D O I
10.4269/ajtmh.2001.64.247
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem(R)/Riamet(R); Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (greater than or equal to 12 years old) with acute. uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine. than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.
引用
收藏
页码:247 / 256
页数:10
相关论文
共 40 条
[1]   An integrated assessment of the clinical safety of artemether-lumefantrine: a new oral fixed-dose combination antimalarial drug [J].
Bakshi, R ;
Hermeling-Fritz, I ;
Gathmann, I ;
Alteri, E .
TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 2000, 94 (04) :419-424
[2]   Cardiac effects of co-artemether (artemether/lumefantrine) and mefloquine given alone or in combination to healthy volunteers [J].
Bindschedler, M ;
Lefèvre, G ;
Ezzet, F ;
Schaeffer, N ;
Meyer, I ;
Thomsen, MS .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2000, 56 (05) :375-381
[3]   FATAL NEUROTOXICITY OF ARTEETHER AND ARTEMETHER [J].
BREWER, TG ;
GRATE, SJ ;
PEGGINS, JO ;
WEINA, PJ ;
PETRAS, JM ;
LEVINE, BS ;
HEIFFER, MH ;
SCHUSTER, BG .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1994, 51 (03) :251-259
[4]  
BUNNAG D, 1991, Southeast Asian Journal of Tropical Medicine and Public Health, V22, P380
[5]   Pharmacokinetics and pharmacodynamics of lumefantrine (benflumetol) in acute falciparum malaria [J].
Ezzet, F ;
van Vugt, M ;
Nosten, F ;
Looareesuwan, S ;
White, NJ .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (03) :697-704
[6]   Population pharmacokinetics and therapeutic response of CGP56697 (artemether plus benflumetol) in malaria patients [J].
Ezzet, F ;
Mull, R ;
Karbwang, J .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1998, 46 (06) :553-561
[7]   Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1-5 years [J].
Hatz, C ;
Abdulla, S ;
Mull, R ;
Schellenberg, D ;
Gathmann, I ;
Kibatala, P ;
Beck, HP ;
Tanner, M ;
Royce, C .
TROPICAL MEDICINE & INTERNATIONAL HEALTH, 1998, 3 (06) :498-504
[8]   A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria [J].
Hien, TT ;
Day, NPJ ;
Phu, NH ;
Mai, NTH ;
Chau, TTH ;
Loc, PP ;
Sinh, DX ;
Chuong, LV ;
Vinh, H ;
Waller, D ;
Peto, TEA ;
White, NJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (02) :76-83
[9]  
HIEN TT, 1993, LANCET, V341, P603
[10]  
Jiao Xiuquing, 1997, Southeast Asian Journal of Tropical Medicine and Public Health, V28, P476