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A pharmacokinetic–pharmacodynamic model of heart rate during cocaine administration in humans
Author(s) -
Noe Dennis A,
Kumor Karen M
Publication year - 1991
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 - 10.1038/clpt.1991.50
Subject(s) - chronotropic , tachyphylaxis , heart rate , pharmacodynamics , pharmacokinetics , medicine , pharmacology , drug , anesthesia , blood pressure
We developed a pharmacokinetic‐pharmacodynamic model of the heart rate response to cocaine consisting of the sum of the baseline heart rate, a chronotropic drug effect, and a conditioned heart rate response. The conditioned response was modeled as having a monoexponential decline. Cocaine's chronotropic effect was modeled as obeying a maximum (E max ) drug‐effect relationship without tachyphylaxis. The model was tested by fitting the kinetic and heart rate data from an earlier study. The data from five subjects in that study were well fit by the model: mean E max , 64 beats/min, and mean drug concentration producing 50% of E max , 838 ng cocaine/ml. The data from the other three subjects in that study were fit well, employing a linear rather than an E max drug effect relationship: mean effect coefficient, 0.035 beats/min/ng cocaine/ml. The findings emphasize the importance of conditioning in the responses to psychoactive drugs. Clinical Pharmacology and Therapeutics (1991) 49, 426–432; doi: 10.1038/clpt.1991.50