Comparative Pharmacokinetics and Bioavailability of Dilacor XR and Cardizem CD in Healthy Volunteers.
The objective of this investigation was to compare the single-dose and steady-state pharmacokinetic profiles of Dilacor XR to Cardizem CD. The study enrolled 24 healthy males and was divided into three parts: a single intravenous 25-mg bolus dose of diltiazem HCl (Cardizem Injectable) followed by a two-way crossover comparison of single and multiple once-daily 240-mg oral doses of Dilacor XR and Cardizem CD. Plasma samples were analyzed for diltiazem using a specific and sensitive HPLC assay. Statistical analysis and deconvolution were performed on the data. A 1- and 3-hour lag time in diltiazem absorption was noted following the administration of Dilacor XR and Cardizem CD, respectively. Statistically significant differences were noted in mean single- and multiple-dose t(max) values with Cardizem CD taking approximately twice as long as Dilacor XR to reach C(max). Dilacor XR was equivalent to Cardizem CD with respect to AUC((0--infty infinity)) and C(max). Equivalent minimum and average steady-state plasma diltiazem concentrations were noted after multiple-dose administration. Deconvolution of the single-dose data also showed similar mean bioavailabilities for the respective formulations but revealed dissimilarities in each product's absorption profile that may reflect observed differences in absorption lag time and t(max).
Argenti
Domenick
D
Rhóne-Poulenc Rorer, Drug Disposition Department, (NW 13) Collegeville, PA 19146, USA.
Huang
Mei-Yung
MY
Heald
Donald
D
Ziemniak
John
J