Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin) in Cambodian children and adults with malaria.
OBJECTIVE
To assess the haemodynamic, electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin (Artekin) fixed combination therapy in uncomplicated malaria.


METHODS
Sixty-two Cambodians (32 children and 30 adults) with falciparum or vivax malaria were given Artekin given as four age-based oral doses over 32 h. Supine and erect blood pressure, the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring. QT intervals were rate-corrected (QTc) using Bazett's formula.


RESULTS
Artekin therapy was well tolerated and all patients responded to treatment. Average parasite and fever clearance times were 19 and 12 h, respectively. The pretreatment mean fall in systolic blood pressure on standing was 8 +/- 6 mmHg and 6-hourly measurements over 72 h showed no significant change (P = 0.48). There was a significant lengthening of the mean QTc to a maximum of 11 ms(0.5) (95% confidence interval 4-18 ms(0.5)) relative to baseline at 24 h (P = 0.003). The maximal QTc prolongation observed in any patient was 53 ms(0.5). There was a mean 0.4 mmol l(-1) reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia (plasma glucose < 3.0 mmol l(-1)) were observed at any time.


CONCLUSIONS
Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults. Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine, no clinically significant cardiovascular or metabolic effects were observed.
Karunajeewa
Harin
H
Medicine Unit (Fremantle Hospital), School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia.
Lim
Chiv
C
Hung
Te-Yu
TY
Ilett
Kenneth F
KF
Denis
Mey Bouth
MB
Socheat
Doung
D
Davis
Timothy M E
TM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D001786:Blood Glucose / Q000032:analysis; D002160:Cambodia / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004341:Drug Evaluation; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000453:epidemiology; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects*; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D001786:Blood Glucose; D004338:Drug Combinations; D011804:Quinolines; D012717:Sesquiterpenes; C039060:artenimol; C034759:piperaquine; D010879:Piperazines