Pharmacokinetics and haemodynamic effect of deacetyl diltiazem (M1) in rabbits after a single intravenous administration

✍ Scribed by Pollen K. F. Yeung; Joe D. Z. Feng; Susan J. Buckley

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 147 KB
• Volume: 19
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199803)19:2<109::aid-bdd84>3.0.co;2-v

✦ Synopsis

Deacetyl diltiazem (M 1 ) is a major metabolite of the widely used calcium antagonist diltiazem (DTZ). In order to study the pharmacokinetic and haemodynamic effects of this metabolite, M 1 was administered as a single 5 mg kg -1 dose intravenously (iv) to New Zealand white rabbits (n = 5) via a marginal ear vein. Blood samples, blood pressure (SBP and DBP), and heart rate (HR) recordings were obtained from each rabbit up to 8 h, and urine samples for 48 h post-dose. Plasma concentrations of M 1 and its metabolites were determined by HPLC. The results showed that the only quantifiable basic metabolite in the plasma was deacetyl N-monodesmethyl DTZ (M 2 ). The t 1/2 and AUC of M 1 and M 2 were 2.19 0.5 and 3.09 1.1 h, and 1300 9200 and 2409 37 ng h mL -1 , respectively. The Cl and Cl r of M 1 were 60 9 10 and 0.81 90.63 mL min -1 kg -1 , respectively. M 1 significantly decreased blood pressure (SBP and DBP) for up to 1 h post-dose (pB0.05), but had no significant effect on the heart rate (p \0.05). The E max and EC 50 as estimated by the inhibitory sigmoidal E max model were 20 9 18% 620 9 310 ng mL -1 , respectively for SBP; 20 98.3% and 4209 160 ng mL -1 for DBP.