Premium
Pharmacokinetics and haemodynamic effect of deacetyl diltiazem (M 1 ) in rabbits after a single intravenous administration
Author(s) -
Yeung Pollen K. F.,
Feng Joe D. Z.,
Buckley Susan J.
Publication year - 1998
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199803)19:2<109::aid-bdd84>3.0.co;2-v
Subject(s) - metabolite , diltiazem , pharmacokinetics , chemistry , hemodynamics , pharmacology , high performance liquid chromatography , heart rate , blood pressure , active metabolite , chromatography , medicine , anesthesia , endocrinology , calcium , biochemistry , organic chemistry
Abstract 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 2.1±0.5 and 3.0±1.1 h, and 1300±200 and 240±37 ng h mL −1 , respectively. The Cl and Cl r of M 1 were 60±10 and 0.81±0.63 mL min −1 kg −1 , respectively. M 1 significantly decreased blood pressure (SBP and DBP) for up to 1 h post‐dose ( p <0.05), 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±18% 620±310 ng mL −1 , respectively for SBP; 20±8.3% and 420±160 ng mL −1 for DBP. © 1998 John Wiley & Sons, Ltd.