Pharmacokinetics of an oral sustained-release diltiazem preparation

✍ Scribed by Kazuo Murata; Hiroshi Yamahara; Masao Kobayashi; Kazuo Noda; Masayoshi Smejima

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 363 KB
• Volume: 78
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600781116

✦ Synopsis

The pharmacokinetics of a new oral sustained-release diltiazem preparation (HER-SR,QD) was investigated in dogs and humans. The mean plasma diltiazem concentration in dogs after oral administration of HER-SR showed a prolonged plasma concentration and a double peak. The bioavailability of HER-SR compared with that of a conventional diltiazem preparation (HER) in dogs was -80%, a value that is relatively close to that of humans. The plasma diltiazem concentrations with a double peak in dogs were analyzed using multifraction absorption models. The HER-SR preparation was apparently divided into two fractions (14.3 and 85.7 mg) in the gastrointestinal tract, each fraction was absorbed at rate constants of 4.560 and 0.1 52 h-', respectively, and the lag time of the slow-release component was 8.3 h. The plasma diltiazem concentration data in humans after repetitive oral administration of HER-SR were also analyzed using multifraction absorption models. The initial amount of the fast-and slow-release components were 14.8 and 85.2 mg, respectively. The absorption rate constants were 0.730 h-' for the fast-release component and 0.060 h-' for the slow-release component. The lag time of absorption for the slow-release component was 6.0 h. The pharmacokinetic parameters were close to those obtained in dogs except for K, , and VdMF. The results confirm that HER-SR has desirable pharmacokinetic characteristics as judged from the simulated plasma diltiazem concentration and the peak-to-trough fluctuation (fluctuation parameters) calculated using the simulated plasma diltiazem concentration. In addition, population pharmacokinetics of HER-SR after repetitive oral administration was examined in humans.