Malaria
Conditions
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.
Interventions
DRUGPrimaquine, R-Primaquine, S-Primaquine, SR Primaquine
Cohort 1: Eighteen individuals (6 per group) Cohort 2: Eighteen individuals (6 per group) Group 1-15 mg of S-Primaquine followed by one-week washout, 15 mg of R-Primaquine followed by one week washout, and 30 mg of RS-Primaquine. Group 2- 15 mg of R-Primaquine followed by one-week washout, 30 mg of RSPQ followed by one week washout, and 15 mg of SPQ. Group 3- 30 mg of RS-Primaquine followed by one week washout,15 mg of SPQ followed by a one week washout, and 15 mg of RPQ.
Sponsors
University of Mississippi, Oxford
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed