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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
36
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.
University of Mississippi
Oxford, Mississippi, United States
Primary outcome: Plasma concentration of parent primaquine and carboyprimaquine following a single dose treatment with primaquine (racemate or enantiomers) not to exceed 45 mg
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Time frame: between 0-24 Hours
Area Under Curve (AUC) for primaquine up to 24 hours after the primaquine administration
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Time frame: between 0-24 hours
Maximum concentration (Cmax) for primaquine up to 24 hours after the primaquine administration
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Time frame: between 0-24 hours
Area Under Curve (AUC) for carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Time frame: between 0-24 hours
Maximum concentration of carboxyprimaquine, the major plasma metabolite of primaquine, up to 24 hours after primaquine administration
This study would provide information on differential pharmacokinetics and metabolism of enantiomers of primaquine in normal human volunteers
Time frame: between 0-24 hours
Maximum concentration of selected metabolites primaquine (other than carboxyprimaquine) up to 24 hours after primaquine administration
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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
Time frame: between 0-24 hours
hemoglobin and methemoglobin levels in the blood after administration of primaquine
To monitor hemoglobin and methemoglobin levels in normal human volunteers treated with single dose of primaquine not to exceed 45 mg
Time frame: 0-72 hours
Genotyping of Cytochrome P-450 (CYP)
To determine correlation between metabolism of primaquine and CYP 2D6 genotype
Time frame: day 0