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Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System
- Source :
- Clinical pharmacokinetics. 57(9)
- Publication Year :
- 2018
-
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 (PKPD) such as lack of efficacy or improper selection of initial dosage. A focused assessment is needed for CNS-acting drugs in first-in-human studies to identify the differences in PKPD from animal models as well as choose the appropriate dose. In this review, we summarize available literature from human studies on the pharmacokinetics and pharmacodynamics 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 pharmacokinetic/pharmacodynamic relationships that may lead to more efficient dose selection in CNS drug development.
- Subjects :
- Intracellular Fluid
Psychosis
Central nervous system
Disease
Bioinformatics
030226 pharmacology & pharmacy
Models, Biological
Article
03 medical and health sciences
0302 clinical medicine
Pharmacotherapy
Pharmacokinetics
Drug Development
Medicine
Animals
Humans
Pharmacology (medical)
Computer Simulation
Tissue Distribution
Pharmacology
business.industry
Brain
Extracellular Fluid
medicine.disease
Clinical trial
medicine.anatomical_structure
Drug development
Pharmacodynamics
business
030217 neurology & neurosurgery
Biomarkers
Central Nervous System Agents
Subjects
Details
- ISSN :
- 11791926
- Volume :
- 57
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Clinical pharmacokinetics
- Accession number :
- edsair.doi.dedup.....66ec20e1467f82a0b2d9fbe025bc7295