Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System

Clinical Pharmacokinetics
Nithya SrinivasAngela D M Kashuba

Abstract

Despite contributing significantly to the burden of global disease, the translation of new treatment strategies for diseases of the central nervous system (CNS) from animals to humans remains challenging, with a high attrition rate in the development of CNS drugs. The failure of clinical trials for CNS therapies can be partially explained by factors related to pharmacokinetics/pharmacodynamics (PK/PD), such as lack of efficacy or improper selection of the initial dosage. A focused assessment is needed for CNS-acting drugs in first-in-human studies to identify the differences in PK/PD from animal models, as well as to choose the appropriate dose. In this review, we summarize the available literature from human studies on the PK and PD in brain tissue, cerebrospinal fluid, and interstitial fluid for drugs used in the treatment of psychosis, Alzheimer's disease and neuro-HIV, and address critical questions in the field. We also explore newer methods to characterize PK/PD relationships that may lead to more efficient dose selection in CNS drug development.

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Citations

Oct 23, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Nithya SrinivasAngela D M Kashuba
Jun 27, 2018·Expert Opinion on Drug Metabolism & Toxicology·Katharine E Stott, William Hope
Jul 15, 2020·Antimicrobial Agents and Chemotherapy·Aaron S DevanathanAngela D M Kashuba
Feb 5, 2021·Clinical Pharmacology and Therapeutics·Aaron S Devanathan, Mackenzie L Cottrell
Jun 19, 2021·Journal of Pharmacokinetics and Pharmacodynamics·Mohammed A A SalehElizabeth C M De Lange
Jul 22, 2021·PloS One·Davide De FrancescoUNKNOWN Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) study
Aug 28, 2021·International Journal of Molecular Sciences·Shiran SuDavid L Brody
Sep 18, 2021·Current Opinion in Infectious Diseases·Aaron J Heffernan, Jason A Roberts

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