Single‐Dose and Steady‐State Pharmacokinetics of Diltiazem Administered in Two Different Tablet Formulations

: Single‐dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assesed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 ± 1.9 and 6.8 ± 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean ± S.D.) values following single dose administration of Cardil® and Cardizem® were 678.4 ± 321.5 and 948.6 ± 580.6 ng · ml‐1 · hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/ AUCCardizem are 0.89 and 0.44‐1.34 respectively. At steady‐state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 ± 2.0 and 6.0 ± 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean ± S.D.) values in steady state of Cardil® and Cardizem® were 880.1 ± 399.8 and 1056.8 ± 509.8 ng · ml‐1 · hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66‐1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single‐dose and the steady‐state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2).