Investigation of bioavailability, pharmacokinetics and safety of new pediatric formulations of artesunate and mefloquine.
The bioavailability/pharmacokinetics of dihydroartemisinin and mefloquine following the oral doses of 4 mg/kg body weight artesunate (Cambodian Pharmaceutical Enterprise) given concurrently with 10 mg/kg body weight oral mefloquine artesunate (Cambodian Pharmaceutical Enterprise) were investigated in 15 healthy Cambodian male volunteers. Both formulations were generally well tolerated. Both produced satisfactory plasma/blood concentration-time profiles. Oral artesunate and mefloquine were rapidly absorbed from gastrointestinal tract with marked inter-individual variation. For the dihydroartemisinin, the median (95% Cl) Cmax of 748 (304-1,470) ng/ml was observed at 1.5 (0.3-3.0) hours (tmax) after drug administration. The median (95% CI) values for AUC0-infinity, lambda(z) and tl/2z were 1.673 (1.08-2.88) microg.h/ml, 0.54(0.24-1.1)/hour and 1.3 (0.6-2.9) hours, respectively. For mefloquine, a median (95% Cl) Cmax of 1,000 (591-1,500) ng/ml was observed at 4 (2-6) hours (tmax) after drug administration. The median (95% CI) value for AUC0-168h was 3.92 (2.88-7.02) microg.h/ml.
Chanthap
L
L
National Center for Parasitological Entomology and Malaria Control Program, Ministry of Health, Cambodia.
Tsuyuoka
R
R
Na-Bangchang
K
K
Nivanna
N
N
Suksom
D
D
Sovannarith
T
T
Socheat
D
D
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077332:Artesunate; D001682:Biological Availability; D004359:Drug Therapy, Combination; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010372:Pediatrics; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol; D015767:Mefloquine