1. Structure of the final PK/PD model.
Structure of the final PK/PD model. A two-compartment model for systemic disposition (“Peripheral d-amphetamine” compartment) applies only to the rat. Pharmacokinetic parameter definitions: Clcsf, clearance from ECF to CSF; Clin, uptake clearance from plasma to brain ECF; Clout, efflux clearance from brain ECF to plasma; Clp, clearance from the central compartment; Q, intercompartmental distribution clearance; Qcsf-plasma, distributional clearance between plasma and CSF; Vb, unbound volume of distribution in the brain; Vc, volume of central compartment; Vcsf, volume of the CSF compartment; Vp, volume of the peripheral compartment. Pharmacodynamic parameter definitions: kin, zero-order rate constant for dopamine release into the synapse; kout, first-order rate constant for dopamine reuptake into the presynaptic nerve terminal; ktol, first-order rate constant for production and dissipation of the moderator response. Buffering of the moderator response owing to dose-dependent increases in the duration and extent of the dopamine effect is indicated by the dashed outlined box, and corresponds to eq. 8a in the text. Circled numbers in the figure correspond to those used in Fig. 1.
Marcel M. van Gaalen et al. J Pharmacol Exp Ther 2019;369:
Copyright © 2019 The Author(s).