Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India.
OBJECTIVE
India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs.


METHODS
This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008.


RESULTS
A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was well-tolerated and no serious adverse events were reported.


CONCLUSIONS
The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.
Neena
N
Valecha
Bina
B
Srivastava
N G
NG
Dubhashi
B H Krishnamoorthy
BH
Rao
Ashwani
A
Kumar
S K
SK
Ghosh
Jai Prakash Narayan
JP
Singh
J R
JR
Kiechel
Bhawna
B
Sharma
V
V
Jullien
A P
AP
Dash
W R J
WR
Taylor
National Institute of Malaria Research, New Delhi, India.
Anupkumar R
AR
Anvikar
D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077332:Artesunate; D003710:Demography; D004359:Drug Therapy, Combination; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018512:Parasitemia; D010963:Plasmodium falciparum / Q000187:drug effects*; D016896:Treatment Outcome; D055815:Young Adult
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D015767:Mefloquine