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Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo by Pollen K.F. Yeung; Angelita Alcos; Tanya Marcoux; Jinglan Tang is a scholarly article available to read on EtoBox.

What is Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo about?

## Abstract **Background:** In order to identify a suitable rodent model for preclinical study of calcium antagonists, the pharmacokinetics and metabolism of one of the prototypes diltiazem (DTZ) in normotensive Sprague Dawley (SDR) was compared with Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) following 5 mg/kg twice daily for five doses given by subcutaneous injection. **Methods:** Pharmacokinetic data were analyzed by standard procedures assuming a one-compartment model with first-order input using Rstrips^®^, and differences between the groups were considered significant when p 0.05). Plasma concentrations of the active metabolites N-desmethyl DTZ (MA), deacetyl DTZ (M1) and deacetyl N-desmethyl DTZ (M2) were significantly higher in the SHR and WKY rats than the SDR, which was attributed to higher DTZ concentrations and also genetic factors. **Conclusions:** Although the differences were mainly quantitative and very small, the study has shown for the first time that the metabolism profiles of DTZ in SHR and WKY rats were closer to humans than SDR, and they may be more preferable rat models to study pharmacokinetic and metabolism studies of DTZ or similar ag

Author

Pollen K.F. Yeung; Angelita Alcos; Tanya Marcoux; Jinglan Tang

Publisher

Walter de Gruyter GmbH

Published

2011

Language

EN