Reference

Radioenzymatic assay of angiotensin-converting enzyme inhibitors in plasma and urine

Radioenzymatic assay of angiotensin-converting enzyme inhibitors in plasma and urine. Swanson, Brian N.; Stauber, Kathe L.; Alpaugh, Walter C.; Weinstein, Stephen H. (Dep. Drug Metab., Squibb Inst. Med. Res., Princeton, NJ 08540, USA). Anal. Biochem., 148(2), 401-7 (English) 1985. CODEN: ANBCA2. ISSN: 0003-2697. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A rapid, sensitive assay for angiotensin converting enzyme (ACE) [9015-82-1] inhibitors is described. Biol. samples were dild. with MeOH to ppt. endogenous ACE and centrifuged. Supernatants were further dild. with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, pH 8. Dild. samples were incubated at 37° with the substrate [3H]hippurylglycylglycine and rabbit lung ACE for 45 min. Acid (1.0 N HCl) was then added, and the product, [3H]hippuric acid, was extd. into a water-immiscible scintillation cocktail. Drug stds. were prepd. in the biol. matrix to correct for drug recovery. A computer program was used to convert radioactivity (dpm) to units of enzyme activity and then correlate enzyme activity with drug concn. The ester prodrugs fosenopril [98048-97-6] and enalapril [75847-73-3] could be assayed down to 4 ng/mL in plasma after ester hydrolysis with NaOH. Drug disposition studies in rats, dogs, and monkeys have demonstrated that the method can be readily adapted to any ACE inhibitor and is suitable for detg. drug bioavailability and pharmacokinetics.

Pharmaceutical compositions comprising the combination of beta blocker and ACE inhibitors

All Rights Reserved. Pharmaceutical compositions comprising the combination of beta blocker and ACE inhibitors. Kharwade, Pramod; Chawla, Manish; Raghuvanshi, Rajeev Singh; Rampal, Ashok (Ranbaxy Laboratories Limited, India). PCT Int. 3930-20-9 and 98048-97-6 are cas registry numbers. These chemicals are also mentioned in this article. Appl. WO 2007010501 A2 25 Jan 2007, 23pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IS, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization). CODEN: PIXXD2. APPLICATION: WO 2006-IB52513 21 Jul 2006. PRIORITY: IN 2005-DE1937 22 Jul 2005. DOCUMENT TYPE: Patent CA Section: 63 (Pharmaceuticals) A once a day pharmaceutical compn. for use in the treatment of cardiovascular disorders includes (a) a first active ingredient comprising a beta blocker; (b) a second active ingredient comprising an ACE inhibitor; and (c) optionally one or more pharmaceutically acceptable excipients. The beta blocker is present in an extended release form and the ACE inhibitor is present in an immediate release form. For example, capsules contained metoprolol succinate, and ramipril which were sepd. by polymer coatings of Et cellulose, Opadry, HPMC, and HPC. .