Pharmaco-electroencephalography and pharmacokinetic/pharmacodynamic modeling in basic research: focus on human pharmacology.
Pharmacokinetic/pharmacodynamic modeling, together with electroencephalography (EEG), have been successfully applied to obtain in vivo pharmacological information of different drugs acting on the central nervous system (CNS) in humans and of the systems with which the drugs interact. Almost all types of variables used to assess the activity of drugs in the human CNS have already been applied in pharmacokinetic/pharmacodynamic research. However, compared with more traditional approaches to quantify the pharmacodynamics of neuropsychotropic drugs, the EEG method has the advantage of being objective, sensitive, continuous and reproducible. The present review focuses mostly on benzodiazepine pharmacology. A selection of some basic aspects that can be covered using pharmaco-EEG and pharmacokinetic/pharmacodynamic modeling from in vivo studies performed in humans in pharmacological research will be introduced: i) determination of the pharmacological characteristics of a compound; ii) comparison of potencies among drugs; iii) comparison of efficacy among drugs; iv) tolerance development; v) metabolite role; vi) enantiomers; vii) drug-drug interactions; viii) circadian rhythms; ix) factors affecting the observed effect; and x) the gain of physiopathological information about the systems with which drugs interact. Looking at the quantity and quality of the results obtained for the benzodiazepines, pharmacokinetic/pharmacodynamic modeling using EEG measures appears to be an ideal tool, and is potentially useful for other drugs acting on the CNS.
Valle
M
M
Centre d'Investigació de Medicaments, Institut de Recerca HSCSP, Departament de Farmacologia i Terapèutica, Universitat Autónoma de Barcelona, Barcelona, Spain.
Barbanoj
M J
MJ
Jané
F
F
D001569:Benzodiazepines / Q000493:pharmacokinetics* / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D006801:Humans; D008954:Models, Biological
D001569:Benzodiazepines