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Development and identification of a multicompartment model for the distribution of adriamycin in the rat

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Author: Sonneveld, P. · Mulder, J.A.
Type:article
Date:1981
Institution: Radiobiologisch Instituut
Source:Journal of Pharmacokinetics and Biopharmaceutics, 5, 9, 577-601
Identifier: 229097
doi: doi:10.1007/BF01061027
Keywords: Animal · Biological Transport · Doxorubicin · Female · Kinetics · Mathematics · Models, Biological · Rats · Rats, Inbred BN · Tissue Distribution

Abstract

The distribution kinetics of adriamycin in the rat were analyzed by using a multicompartment mathematical model. The set of a priori unknown model parameters, the drug rate constants, were estimated from 48 hr multicompartment drug distribution data by applying multivariate system identification techniques. Simultaneously, the information in all the measurements is exploited for the calculation of drug concentration time curves of each compartment of the model. No quantitative a priori information is required in the form of blood flow or membrane transport limitations. This approach requires only qualitative a priori biological information in the form of a mathematical model structure and successfully analyzes complex multidimensional pharmacokinetics. It results in a compact and realistic representation of physiologic drug transport processes. Chemicals/CAS: doxorubicin, 23214-92-8, 25316-40-9; iron 59, 14596-12-4; Doxorubicin, 23214-92-8