Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers, Study 1

Development of Safer Drugs for Malaria in U.S. Troops, Civilian Personnel, and Travelers: Clinical Evaluation of Primaquine Enantiomer

To investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers. The specific aim is the comparative evaluation of the metabolism, pharmacokinetic behavior, and tolerability of the isomers of PQ (RPQ and SPQ and the racemic mixture RSPQ) in normal healthy human volunteers.

The primary objective of this project is to investigate the comparative tolerability, metabolism and pharmacokinetics of individual enantiomers of PQ in healthy human volunteers.

The overall approach is as follows: in 36 healthy volunteers with documented normal G6PD activity, we will administer a single oral dose of RPQ, SPQ, or RSPQ. At various times after dosing, we will draw blood samples, in which we will record the plasma levels of the parent drugs, along with plasma and urinary metabolites. The comparative pharmacokinetics, tolerability and hematological effects of these two enantiomers and the racemate will be assessed.

Inclusion Criteria:

• Adults (18-60 years of age)
• Informed consent
• Healthy

Exclusion Criteria:

• Known history of liver, kidney or hematological disease;
• known history of cardiac disease, arrhythmia, QT prolongation;
• Autoimmune disorder;
• Report of an active infection;
• Evidence of G6PD deficiency