A Population Pharmacokinetic Analysis of Dextroamphetamine in the Plasma and Hair of Healthy Adults.
OBJECTIVE
Hair is an attractive matrix for amphetamine drug testing; however, little is known about the rate at which amphetamines are deposited into hair. Therefore, the purpose of this study was to determine the pharmacokinetics of oral dextroamphetamine in plasma and quantify the rate of deposition into hair in healthy adults using a linked population pharmacokinetic model.


METHODS
Healthy adults >18 years of age received dextroamphetamine 10 mg orally for 7 days. Plasma samples were collected over 48 h following the final dose, and hair was collected 5 weeks following the first dose. NONMEM 7.2 was used to estimate dextroamphetamine oral absorption rate constant, apparent clearance and volume of distribution of the plasma compartment, the plasma to hair incorporation rate constant, and the apparent volume of distribution in the hair compartment.


RESULTS
Dextroamphetamine pharmacokinetics were well-described by a one-compartment model with combined additive and proportional error for the plasma compartment, which was linked to a single compartment for the hair. Apparent clearance and volume of distribution in the plasma compartment were scaled by current body weight (centered on the mean). Melanin hair concentration was included as a significant covariate on the hair compartment. Absorption rate constant, clearance, and volume of distribution for the plasma compartment were estimated as 0.527 h(-1) (95% CI 0.467-0.586), 28.7 L/h (95% CI 27.1-30.3), and 377 L (95% CI 326-428), respectively. The incorporation rate constant from plasma to hair was 1.60e(-6) h(-1) (95% CI 1.06e(-6)-2.14e(-6)) and apparent volume of distribution in hair was 17.7 mg (95% CI 12.5-22.8).


CONCLUSIONS
A one-compartment plasma model linked to a single compartment for hair successfully described the pharmacokinetics of dextroamphetamine in healthy adults. The volume of distribution and clearance of dextroamphetamine increased with weight, and the volume of distribution of the hair compartment increased with greater melanin concentrations.
Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.
Jessica K
JK
Roberts
Center for Human Toxicology, Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
Sarah F
SF
Cook
Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, 295 Chipeta Way, Salt Lake City, UT, 84108, USA.|Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
Chris
C
Stockmann
Center for Human Toxicology, Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
Douglas E
DE
Rollins
Center for Human Toxicology, Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.|Division of Medical Laboratory Sciences, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Diana G
DG
Wilkins
Division of Clinical Pharmacology, Department of Pediatrics, School of Medicine, University of Utah, 295 Chipeta Way, Salt Lake City, UT, 84108, USA. catherine.sherwin@hsc.utah.edu.
Catherine M T
CM
Sherwin
D000328:Adult; D003913:Dextroamphetamine / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D006197:Hair / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008543:Melanins / Q000378:metabolism; D008954:Models, Biological; D015813:Substance Abuse Detection / Q000379:methods; D055815:Young Adult
D008543:Melanins; D003913:Dextroamphetamine