Cyclopentenyl cytosine : interspecies predictions based on rodent plasma and urine kinetics

A hybrid compartmental-physiological model for cyclopentenyl cytosine (CPE-C) is designed on the basis of early limited rodent pharmacokinetic data. Application of model independent pharmacokinetics and biochemical knowledge was first used to conceptualize such a model. The approach was to scale the...

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Bibliographic Details
Published in:Investigational new drugs 1991-02, Vol.9 (1), p.9-17
Main Authors: ZAHARKO, D. S, KELLEY, J. A, TOMASZEWSKI, J. E, HEGEDUS, L, HARTMAN, N. R
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - blood
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - urine
Biological and medical sciences
Computer Simulation
Cytidine - analogs & derivatives
Cytidine - blood
Cytidine - pharmacokinetics
Cytidine - urine
Dogs
Drug Administration Schedule
General aspects
Injections, Intravenous
Medical sciences
Mice
Models, Biological
Pharmacology. Drug treatments
Rats
Species Specificity
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Summary:A hybrid compartmental-physiological model for cyclopentenyl cytosine (CPE-C) is designed on the basis of early limited rodent pharmacokinetic data. Application of model independent pharmacokinetics and biochemical knowledge was first used to conceptualize such a model. The approach was to scale the physiological parameters of the model (compartmental clearances) and keep constant the anatomic parameters of the model (compartment volumes). Scaling of physiological mechanisms was based on body weight/surface area ratios. Using these principles, simulations with the model can reasonably anticipate the in vivo behavior of (CPE-C) in several species (mouse, rat, dog). The model is useful in understanding species differences in pharmacokinetic behavior of CPE-C.
ISSN:0167-6997
1573-0646
DOI:10.1007/BF00194539