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PK/PD modeling of the interaction between IV scopolamine (SCP) and physostigmine (PHY) in healthy elderly volunteers
Author(s) -
Men Y.,
Wesnes K.,
Venitz J.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.009
Subject(s) - physostigmine , scopolamine , phy , pharmacology , medicine , chemistry , computer science , acetylcholine , physical layer , telecommunications , wireless
Aims 1. To assess the PK/PD interaction between IV SCP and PHY in elderly subjects; 2. To estimate in vivo muscarinic receptor affinities for SCP. Methods In a randomized, placebo‐controlled, four‐way crossover clinical trial, sixteen volunteers (> 65 years) received 6.7μg/kg IV SCP/placebo, followed after 60 minutes by 6.7μg/kg IV PHY/placebo. An integrated SCP PK/PD model was used to simultaneously fit the plasma concentration and PD endpoints (heart rate, BPCHR, saliva flow, SF, simple reaction time, SRT, numerical working memory, NWM). A competitive PD model described the PD interaction between SCP and PHY. Results SCP and PHY PK profiles fit two‐ and one compartment models, respectively. Median PK and PD parameter estimates (n= 16) are as follows: (see Table) Conclusions PHY IC 50 s were estimated successfully: IC 50 CNS