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20.02.2018 | Review Article | Ausgabe 9/2018

Clinical Pharmacokinetics 9/2018

Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System

Zeitschrift:
Clinical Pharmacokinetics > Ausgabe 9/2018
Autoren:
Nithya Srinivas, Kaitlyn Maffuid, Angela D. M. Kashuba
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s40262-018-0632-y) contains supplementary material, which is available to authorized users.

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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Zusatzmaterial
Supplementary material 1 (DOCX 17 kb)
40262_2018_632_MOESM1_ESM.docx
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