Publication Date:
1992-09-25
Description:
Peptidic renin inhibitors have been poorly absorbed across the intestine or rapidly eliminated by the liver and have been reported to have oral bioavailabilities of less than 2%. A peptide-based renin inhibitor, A-72517 (molecular mass of 706 daltons), was devised that has oral bioavailabilities of 8, 24, 32, and 53% in the monkey, rat, ferret, and dog, respectively. Dose-related reductions in blood pressure, plasma renin activity, and plasma angiotensin II in parallel with increased plasma drug concentrations were observed after oral administration of A-72517 to conscious, salt-depleted dogs. Thus, peptide-based molecules of sizable molecular mass can be absorbed intact into the systemic circulation of animals. These findings support the potential of peptide-based drugs for oral administration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kleinert, H D -- Rosenberg, S H -- Baker, W R -- Stein, H H -- Klinghofer, V -- Barlow, J -- Spina, K -- Polakowski, J -- Kovar, P -- Cohen, J -- New York, N.Y. -- Science. 1992 Sep 25;257(5078):1940-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abbott Laboratories, Abbott Park, IL 60064.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1411510" target="_blank"〉PubMed〈/a〉
Keywords:
Administration, Oral
;
Animals
;
Biological Availability
;
Hemodynamics/drug effects
;
Peptides
;
Piperazines/chemistry/pharmacokinetics/*pharmacology
;
Protease Inhibitors/chemistry/*metabolism/pharmacokinetics
;
Renin/*antagonists & inhibitors
;
Structure-Activity Relationship
;
Thiazoles/chemistry/pharmacokinetics/*pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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