KW-6356 is a selective antagonist and inverse agonist of the adenosine A2A receptor. The primary aim of the present analysis was to characterize the pharmacokinetics (PK) of KW-6356 and its active metabolite M6 in healthy subjects and patients with Parkinson's disease (PD). We pooled concentration-time data from healthy subjects and patients with PD who were administered KW-6356. Using these data, we developed a population PK model by sequentially fitting the KW-6356 parameters followed by the M6 parameters. A first-order absorption with a 1-compartment model for KW-6356 and a 1-compartment model for M6 best described the profiles. The covariates included in the final models were food status (fed/fasted/unknown) on first-order absorption rate constant, baseline serum albumin level on apparent clearance of KW-6356, and baseline body weight on apparent volume of distribution of KW-6356 and apparent clearance of M6. No covariate had a clinically meaningful impact on KW-6356 or M6 exposure.
Adenosine A2 Receptor Antagonists , Healthy Volunteers , Models, Biological , Parkinson Disease , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Adenosine A2 Receptor Agonists/pharmacokinetics , Adenosine A2 Receptor Agonists/administration & dosage , Adenosine A2 Receptor Agonists/pharmacology , Adenosine A2 Receptor Antagonists/pharmacokinetics , Adenosine A2 Receptor Antagonists/administration & dosage , Adenosine A2 Receptor Antagonists/pharmacology , Administration, Oral , Antiparkinson Agents/pharmacokinetics , Antiparkinson Agents/administration & dosage , Drug Administration Schedule , Parkinson Disease/drug therapy , Receptor, Adenosine A2A/metabolism
