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

• Published in: Investigational new drugs Vol. 9; no. 1; pp. 9 - 17
• Main Authors: ZAHARKO, D. S, KELLEY, J. A, TOMASZEWSKI, J. E, HEGEDUS, L, HARTMAN, N. R
• Format: Journal Article
• Language: English
• Published: Dordrecht Kluwer 01-02-1991
• 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; Fissipedia; Carnivora; Intravenous administration; Rat; Computer simulation; Rodentia; Prediction; Compartment model; Species specificity; Pyrimidine base derivatives; Vertebrata; Mammalia; Bolus injection; Mouse; Animal; Pharmacokinetics; Dog
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/BF00194539

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.