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Titolo:
Pharmacokinetic-pharmacodynamic modelling of behavioural responses
Autore:
Della Paschoa, OE; Kruk, MR; Danhof, M;
Indirizzi:
LeidensAmsterdam Ctr Drug Res, Div Pharmacol, NL-2300 RA Leiden, Netherland Leiden Amsterdam Ctr Drug Res Leiden Netherlands NL-2300 RA , Netherland Leiden0Amsterdam Ctr Drug Res, Div Med Pharmacol, Ethopharmacol Grp, NL-230 Leiden Amsterdam Ctr Drug Res Leiden Netherlands NL-2300 RA Grp, NL-230
Titolo Testata:
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
fascicolo: 2, volume: 23, anno: 1998,
pagine: 229 - 236
SICI:
0149-7634(199812)23:2<229:PMOBR>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOSE-EFFECT RELATIONSHIP; POPULATION PHARMACOKINETICS; RECEPTOR ANTAGONISTS; RATS; EPILEPSY; DRUGS; ANTICONVULSANT; TOLERANCE; WARFARIN; ANXIETY;
Keywords:
PK/PD modelling; behavioural measures; data acquisition; ethopharmacology; ultrasonic vocalizations; buspirone; concentration-effect relationship;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Danhof, M LeidenNetherlandsCtr Drug Res, Div Pharmacol, POB 9503, NL-2300 RA Leiden, Leiden Amsterdam Ctr Drug Res POB 9503 Leiden Netherlands NL-2300 RA
Citazione:
O.E. Della Paschoa et al., "Pharmacokinetic-pharmacodynamic modelling of behavioural responses", NEUROSCI B, 23(2), 1998, pp. 229-236

Abstract

Drug concentrations at the site of action in studies on behavioural pharmacology, are seldom constant. Therefore, observed changes in behaviour can be due to the natural time course of behavioural processes, but equally to changes in drug concentration, and it is therefore crucial to separate the former from the latter. One solution is keeping drug concentrations constant. However, one can also exploit the variation in drug concentration caused by absorption, distribution and elimination of a drug. This is done by simultaneous measurement of drug effect and concentration, while the drug enters and leaves a biologically relevant compartment, such as blood or cerebrospinal fluid. The concept of determining concentration-effect curves in individual animals, by monitoring in parallel drug effect and changes in concentration in one single experiment, has not yet found wide application in behavioural studies. The fact that behavioural processes, like any other physiological process, change over time, may have contributed to the scarcity ofpharmacokinetic-pharmacodynamic (PK/PD) studies in behavioural pharmacology. However, there are now mathematical techniques that allow PK/PD modelling even if the effect parameter changes over time or cannot be properly assessed in every instance. Here we use PK/PD modelling to characterize fear-induced ultrasonic vocalizations and the anxiolytic effect of buspirone. Thisapproach reduces the number of animals required to assess concentration-effect relationships. More importantly, it allows the identification of differences in individual drug response over a wide range of concentrations. Consequently, we suggest that PK/PD modelling can be used as a tool to study drug-induced changes in behavioural response. An introduction in PK/PD modelling is presented. (C) 1998 Elsevier Science B.V. All rights reserved.

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Documento generato il 19/09/20 alle ore 11:24:34