Pharmacokinetic and Pharmacodynamic Study of Mefloquine and Dihydroartemisinin-Piperaquine in Healthy Subjects

Inclusion Criteria: 1. Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination. 2. Males and Females non-smoker aged between 18 years to 60 years. 3. Males and Females weight between 36-75 kilograms. 4. A female is eligible to enter and participate in this study if she is: * of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy * or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels \>40 mIU/mL or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy * or of childbearing potential, has a negative serum pregnancy test at screening and prior to start the study drug in each period, and abstain from sexual intercourse or agrees to using effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study until completion of the follow-up procedures 5. A male is eligible to enter and participate in this study if he: agrees to abstain from (or use a condom during) sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures. 6. Provide a signed and dated written informed consent prior to study participation. 7. Normal electrocardiogram (ECG) with QTc \<450 msec. 8. Willingness and ability to comply with the study protocol for the duration of the trial. Exclusion Criteria: 1. Females who are pregnant, trying to get pregnant, or are lactating. 2. The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions. 3. A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening. 4. Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points (heart failure, hypokalemia) or with a family history of sudden cardiac death. 5. A creatinine clearance \<70 mL/min as determined by Cockcroft-Gault equation: Creatinine clearance (CLcr (mL/min)) = (140 - age) \* Wt / (72 \* Scr) (multiply answer by 0.85 for females) Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dL \[Cockcroft, 1976\]. 6. History of alcohol or substance abuse or dependence within 6 months of the study. 7. Use of prescription or non-prescription drugs except paracetamol at doses of up to 2 grams/day, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 times the drug half-life (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise subject safety; the investigator will take advice from the manufacturer representative as necessary. 8. The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-life, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication. 9. The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to the first dose of study medication until collection of the final pharmacokinetic sample during each regimen. 10. Subjects who have donated blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period. Note: This does not include plasma donation. 11. Subjects who have a history of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the trial. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled. 12. Lack of suitability for participation in this study, including but not limited to, unstable medical conditions, systemic disease manifested by tendency to granulocytopenia e.g. rheumatoid arthritis and lupus erythematosus that in the opinion of the investigator would compromise their participation in the trial. 13. Aspartate transaminase (AST) or Alanine transaminase (ALT) \>1.5 upper limit of normal (ULN) 14. Subjects with history of renal disease, hepatic disease, and/or cholecystectomy 15. History of antimalarial drugs use including but not limited to mefloquine, chloroquine, primaquine, artesunate, piperaquine and pyronaridine treatment within 3 months. 16. Subject who received quinacrine in last 30 days.