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Pharmacodynamics of promethazine in human subjects
Author(s) -
Gatlin K.,
Boyd J. L.,
Wang Z.,
Das H.,
Putcha L.
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.2004.12.020
Subject(s) - pharmacodynamics , promethazine , medicine , pharmacology , placebo , sedation , effects of sleep deprivation on cognitive performance , cognition , pharmacokinetics , anesthesia , psychiatry , alternative medicine , pathology
Background Promethazine (PMZ) is the drug of choice for the treatment of space motion sickness in astronauts. Side effects of PMZ include sedation, dizziness and cognitive performance impairment. We studied the pharmacodynamics (PD) of PMZ and validated methods for evaluating cognitive performance effects. Methods PMZ (12.5, 25, and 50 mg) or placebo was administered by IM injection to human subjects in a randomized, double‐blind treatment design in a hospital setting. Samples and data were collected for 72h post dose. PD evaluation was performed using several performance tests including WinSCAT ( W indows‐based S pace C ognitive A ssessment T est) on a laptop computer and ARES ( A NAM R eadiness E valuation S ystem) on a PDA. Plasma concentrations of PMZ were measured using a LC/MS method. Results A linear correlation between PMZ concentration and cognitive performance parameters (p<0.01) was observed. Test accuracy decreased and both test completion time and response time increased significantly with increasing plasma PMZ concentration. Conclusions Concentration‐dependent decrements in cognitive performance were associated with PMZ. WinSCAT and ARES are sensitive tools for the assessment PMZ PD and may be suitable for evaluating other neuroactive drugs. Clinical Pharmacology & Therapeutics (2005) 77 , P33–P33; doi: 10.1016/j.clpt.2004.12.020