Description of the time course of the prolactin suppressant effect of the dopamine agonist CQP201-403 by an integrated pharmacokinetic-pharmacodynamic model.
Six male volunteers (mean age 24 years) received a single oral dose of 0.025 mg CQP201-403 and placebo in a randomised double-blind crossover design. Fifteen plasma samples were collected over 48 h and were assayed by radioimmunoassay for drug substance and prolactin (PRL). Three of the samples were drawn during sleep on the first study day. The pharmacological effect (E%) of CQP201-403 was expressed as reduction in plasma PRL levels. The pharmacokinetic (PK)-pharmacodynamic (PD) model consisted of two kinetic compartments and an effect compartment linked to the central compartment. A sigmoid Emax model (Hill equation) described the relationship between the drug concentration in the effect compartment and E%. Curve-fitting of PK and PD data provided individual parameter estimates which served to generate computer-simulated PK and PD profiles after single and multiple doses in order to: investigate the in vivo concentration-effect relationship; evaluate the consequence of dosage reduction on the steady-state PD profile; and study the robustness of the response to changes in drug potency and bioavailability.
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004873:Ergolines / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D011388:Prolactin / Q000097:blood*; D011863:Radioimmunoassay; D011897:Random Allocation; D012984:Software; D013997:Time Factors
D004873:Ergolines; C049850:CQP 201-403; D011388:Prolactin