Quantitative structure-pharmacokinetic relationship modelling: apparent volume of distribution

Ghafourian, Taravat, Barzegar-Jalali, Mohammad, Hakimiha, Nasim and Cronin, Mark T D (2004) Quantitative structure-pharmacokinetic relationship modelling: apparent volume of distribution. Journal of Pharmacy and Pharmacology, 56 (3). pp. 339-350. ISSN 0022-3573

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The purpose of this study was to develop a quantitative structure-activity relationship (QSAR) for the prediction of the apparent volume of distribution (Vd) in man for a heterogeneous series of drugs. The relationship of many computed, and some experimental, structural descriptors with Vd, and the Vd corrected for protein binding (unbound Vd), was investigated. Models were constructed using stepwise regression analysis for all the 70 drugs in the dataset, as well as for acidic drugs and basic drugs separately. The predictive power of the models was assessed using half the chemicals as a test set, and revealed that the models for Vd yielded lower prediction errors than those constructed for the unbound Vd (mean fold error of 2.01 for Vd compared with 2.28 for unbound Vd). Moreover, the separation of the compounds into acids and bases did not reduce the prediction error significantly. © 2004 The Authors.

Item Type: Article
Keywords: acetanilide; alprazolam; amfebutamone; anesthetic agent; barbituric acid derivative; benzodiazepine derivative; bromazepam; bupivacaine; carbamazepine; central nervous system agents; chloral hydrate; chlordiazepoxide; chlorphentermine; clobazam; clomipramine; clonazepam; clorazepate; desipramine; doxepin; ethchlorvynol; fluoxetine; glutethimide; haloperidol; hydantoin derivative; imipramine; narcotic analgesic agent; nonsteroid antiinflammatory agent; succinimide derivative; tricyclic antidepressant agent; unindexed drug, acidity; analytical error; article; controlled study; distribution volume; drug determination; drug protein binding; drug structure; partition coefficient; pH measurement; physical chemistry; prediction; quantitative structure activity relation; regression analysis; statistical model; validation process, Algorithms; Humans; Hydrogen-Ion Concentration; Models, Biological; Pharmaceutical Preparations; Pharmacokinetics; Protein Binding; Quantitative Structure-Activity Relationship
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Taravat Ghafourian
Date Deposited: 29 Nov 2017 16:28
Last Modified: 02 Jul 2019 17:18
URI: http://sro.sussex.ac.uk/id/eprint/64160

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