Disposition of zofenopril calcium in healthy subjects

✍ Scribed by Sampat M. Singhvi; James E. Foley; David A. Willard; Richard A. Morrison

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 457 KB
• Volume: 79
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600791105

✦ Synopsis

Zofenopril calcium (1) is a prodrug that is hydrolyzed in vivo to the active angiotensin-converting enzyme (ACE) inhibitor SQ 26,333 (2). In a two-way crossover study, six healthy male subjects (age range 25-36 years) each received an iv 11.2-mg dose of ['4C]SQ 26,703 (14C-3; the L-arginine salt of 2) and an oral 10-mg (equimolar) dose of 14C-l. After the iv dose of I4C-3, the 0-96-h recovery of radioactivity averaged 76 and 16% of the dose in urine and feces, respectively, indicating substantial biliary secretion. After the oral dose of l4C-l, excretion of radioactivity averaged 70% (urine) and 26% (feces). Negligible amounts of 1 were present in urine, indicating complete hydrolysis of the orally administered prodrug. The oral absorption of 1 was almost complete and the oral bioavailability of 2 averaged -70%. The terminal elimination half-life for 2 after the iv dose averaged 5.5 h. Whole body clearance, renal clearance, nonrenal clearance, and Vd, averaged 1 1.4, 3.1, and 8.3 mUmin/kg and 1.3 Ukg, respectively. These data indicated that 2 is eliminated by the kidney as well as the liver, is extensively