Metabolism and Pharmacokinetics of Primaquine Enantiomers in Human Volunteers, Study 1
- Conditions
- Malaria
- Interventions
- Drug: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine
- Registration Number
- NCT02898779
- Lead Sponsor
- University of Mississippi, Oxford
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
- Adults (18-60 years of age)
- Informed consent
- Healthy
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 1 ( Primaquine Low Dose) Primaquine, R-Primaquine, S-Primaquine, SR Primaquine Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers. Cohort 1 (Low Dose Level)- single dose of 15 mg of S-Primaquine and 15 mg of R-Primaquine compared to 30 mg RS-Primaquine over 24 hours. Participants will cross-over after a one week wash-out period. Cohort 2 (Primaquine High Dose) Primaquine, R-Primaquine, S-Primaquine, SR Primaquine Interventions: Primaquine, R-Primaquine, S-Primaquine, SR Primaquine A single center, prospective, cross-over, randomized phase 1 trial. Thirty-six participants, enrolled into a two cohort pharmacokinetic study evaluating two dose levels of primaquine isomers. Cohort 2 (High Dose Level)-single dose of 22.5 mg of S-Primaquine and 22.5 mg of R-Primaquine compared to 45 mg RS-Primaquine over 24 hours. Participants will cross-over among the treatment arms following a one week wash-out period between each.
- Primary Outcome Measures
Name Time Method Primary outcome: Plasma concentration of parent primaquine and carboyprimaquine following a single dose treatment with primaquine (racemate or enantiomers) not to exceed 45 mg between 0-24 Hours This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
- Secondary Outcome Measures
Name Time Method Maximum concentration of selected metabolites primaquine (other than carboxyprimaquine) up to 24 hours after primaquine administration between 0-24 hours This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers. The exact nature of these metabolites will be determined from previous animal and human studies
Area Under Curve (AUC) for primaquine up to 24 hours after the primaquine administration between 0-24 hours This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Maximum concentration of carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration between 0-24 hours This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Maximum concentration (Cmax) for primaquine up to 24 hours after the primaquine administration between 0-24 hours This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Area Under Curve (AUC) for carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration between 0-24 hours This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
hemoglobin and methemoglobin levels in the blood after administration of primaquine 0-72 hours To monitor hemoglobin and methemoglobin levels in normal human volunteers treated with single dose of primaquine not to exceed 45 mg
Genotyping of Cytochrome P-450 (CYP) day 0 To determine correlation between metabolism of primaquine and CYP 2D6 genotype
Trial Locations
- Locations (1)
University of Mississippi
🇺🇸Oxford, Mississippi, United States