Development of a Semimechanistic Pharmacokinetic-Pharmacodynamic Model Describing Dextroamphetamine Exposure and Striatal Dopamine Response in Rats and Nonhuman Primates following a Single Dose of Dextroamphetamine

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 369; no. 1; pp. 107 - 120
• Main Authors: van Gaalen, Marcel M, Schlumbohm, Christina, Folgering, Joost H, Adhikari, Saugat, Bhattacharya, Chandrali, Steinbach, Douglas, Stratford, Robert E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2019
• Subjects: Animals; Dextroamphetamine - adverse effects; Dextroamphetamine - pharmacokinetics; Dextroamphetamine - pharmacology; Dopamine - metabolism; Kinetics; Macaca fascicularis; Male; Neostriatum - drug effects; Neostriatum - metabolism; Rats; Safety; BBB; D2R; CNS; ECF; PKC; MS/MS; PFC; PD; DAT; CSF; NHP; AIC; PK

Acute central nervous system exposure to dextroamphetamine (D-amphetamine) elicits a multitude of effects, including dual action on the dopamine transporter (DAT) to increase extracellular dopamine, and induction of a negative feedback response to limit the dopamine increase. A semimechanistic pharm...