IngentaConnect Interspecies Scaling of Cimetidine-Theophylline Pharmacokinetic I...

Authors: Gascón A.R.¹; Calvo B.¹; Hernández R.M.¹; Domínguez-Gil A.²; Pedraz J-L.³

Source: Pharmaceutical Research, Volume 11, Number 7, July 1994 , pp. 945-950(6)

Publisher: Springer

Abstract:

The aim of the present study was the use of an interspecies scaling approach to predict drug interactions during preclinical drug disposition studies. Theophylline and cimetidine were selected because of their documented interaction. The literature was searched for pharmacokinetic data of intravenously administered theophylline alone and in the presence of cimetidine in humans, dogs and rats. Further, we determined the theophylline-cimetidine drug interaction in rabbits. Application of allometric equations to the pharmacokinetic parameters and the conversion of chronological time into pharmacokinetic time allowed us to obtain the complex Dedrick plot for theophylline when administered alone or in combination with cimetidine. A superimposable kinetic profile was obtained for the plasma levels of theophylline in all species studied, both with and without cimetidine. From the terminal phase of the curves it is possible to calculate the elimination half-life: 2.69 apolisychrons for theophylline when it is administered alone and 3.86 apolisychrons when it is administered in combination with cimetidine. This 43% increase in t_1/2 is similar to the increase in the elimination half-life of theophylline in humans when it is administered after pretreatment with cimetidine. These results show that an interspecies scaling approach may be useful to predict the effect of interactions in humans from the results obtained in preclinical research with new drugs.

Keywords: interspecies scaling; drug interactions; theophylline; cimetidine

Language: English

Document Type: Regular paper

Affiliations: 1: Laboratory of Pharmacy and Pharmaceutical Technology. University of the Basque Country, Vitoria. Spain 2: Department of Pharmacy and Pharmaceutical Technology. University of Salamanca. Salamanca. Spain. 3: Laboratory of Pharmacy and Pharmaceutical Technology. University of the Basque Country, Vitoria. Spain. To whom correspondence should be addressed.

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Interspecies Scaling of Cimetidine–Theophylline Pharmacokinetic Interaction: Interspecies Scaling in Pharmacokinetic Interactions