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- Title
Population Pharmacokinetics of the Novel Adenosine A<sub>2A</sub> Antagonist/Inverse Agonist KW‐6356 and Its Active Metabolite Following Single and Multiple Oral Administration in Healthy Individuals and Patients with Parkinson's Disease.
- Authors
Tayama, Tomonori; Okada, Hiroki; Ogawa, Kotoko; Marsteller, Douglas; Maeda, Hiroshi; Hruska, Matthew W.; Kagawa, Yoshiyuki
- Abstract
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.
- Subjects
PARKINSON'S disease; ORAL drug administration; ADENOSINES; PHARMACOKINETICS; SERUM albumin; BODY weight
- Publication
Clinical Pharmacology in Drug Development, 2024, Vol 13, Issue 5, p549
- ISSN
2160-763X
- Publication type
Article
- DOI
10.1002/cpdd.1359