Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo
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Pollen K.F. Yeung
,
Angelita Alcos
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.
Results: Plasma concentrations of DTZ were higher in the SHR than the normotensive SDR and WKY rats, although the differences did not reach statistical significance (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 agents.
©2011 by Walter de Gruyter Berlin Boston
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Artikel in diesem Heft
- Review
- Theoretical prediction of drug-receptor interactions
- Minireview
- Moving out: from sterol transport to drug resistance – the ABCG subfamily of efflux pumps
- Original Articles
- Gene dose effect of NAT2 variants on the pharmacokinetics of isoniazid and acetylisoniazid in healthy Chinese subjects
- Comparing pharmacokinetics and metabolism of diltiazem in normotensive Sprague Dawley and Wistar Kyoto rats vs. spontaneously hypertensive rats in vivo
- Potential pharmacodynamic drug-drug interaction between concomitantly administered lisinopril and diclofenac sodium: a call for appropriate management in hypertensive osteoarthritic patients
- Case Report
- Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen
