Document Detail

What intervals in oral therapy of isosorbide dinitrate in various doses are sufficient to prevent nitrate tolerance?
MedLine Citation:
PMID:  11208406     Owner:  NLM     Status:  MEDLINE    
INTRODUCTIONS: The organic nitrates are effective anti-anginal drugs during initial treatment, but their therapeutic value is compromised by the rapid development of tolerance during sustained therapy. The only widely accepted method of preventing tolerance is the use of intermittent administration, but without specifying to what extent the length of interval is dependent on type and dose of nitrate. The aim of this study was to evaluate how long periods free of nitrates are sufficient to prevent tolerance in long-term therapy with oral sustained-release isosorbide dinitrate (ISDN). MATERIAL AND METHODS: In a double-blind study, 38 patients with stable angina, received ISDN: 40 mg, 80 mg and 120 mg or placebo in the first ingestion (1st) and in long-term therapy in four 7 day phases: 4-times-daily (4x), 3-times-daily (3x) with 12 h nitrate-free interval, twice-daily (2x) with 18 h interval and once-daily (1x). After 1st and on the last day of each long-term phases, exercise tests with the analysis of walking times: total, to angina and to ischaemia (WTI) were performed: preceding ingestion, 2 h and 6 h after. RESULTS: Six hours after 1st all doses WTI improved significantly in comparison to placebo (p < 0.0001): 40 mg by 52.5%, 80 mg by 66.0% and 120 mg by 58.4%. None of the ISDN doses improved significantly WTI in 4x phase; in 3x, only 40 mg by 12.1% (p < 0.05); in 2x, only 80 mg by 22.3% (p < 0.05) and in once-daily, 80 mg by 27.2% and 120 mg by 36.2% (p < 0.01). CONCLUSION: 12 h nitrate-free interval is sufficient in order to prevent tolerance in long-term treatment of sustained-release ISDN with 40 mg dose, 18 h with 80 mg and 24 h with 120 mg doses.
M Kośmicki; Z Sadowski; H Szwed; I Kowalik
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Medical science monitor : international medical journal of experimental and clinical research     Volume:  6     ISSN:  1234-1010     ISO Abbreviation:  Med. Sci. Monit.     Publication Date:    2000 Jul-Aug
Date Detail:
Created Date:  2001-03-05     Completed Date:  2001-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9609063     Medline TA:  Med Sci Monit     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  763-8     Citation Subset:  IM    
Department of Ischaemic Heart Diseases, National Institute of Cardiology, ul. Spartańska 1, 02-637 Warsaw, Poland.
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MeSH Terms
Administration, Oral
Angina Pectoris / drug therapy*,  physiopathology
Cross-Over Studies
Delayed-Action Preparations
Double-Blind Method
Drug Administration Schedule
Drug Tolerance
Exercise Test
Isosorbide Dinitrate / administration & dosage*
Middle Aged
Time Factors
Vasodilator Agents / administration & dosage*
Reg. No./Substance:
0/Delayed-Action Preparations; 0/Vasodilator Agents; 87-33-2/Isosorbide Dinitrate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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