PMID: 2498105Jan 1, 1989Paper

Lack of effect of asymmetrical dosage timing of isosorbide-5-mononitrate on nitrate tolerance during long-term administration

European Journal of Clinical Pharmacology
L O HughesE B Raftery

Abstract

Isosorbide 5-mononitrate is an active metabolite of isosorbide dinitrate and possesses many theoretical advantages over its parent drug. However, the development of partial tolerance has been demonstrated when the drug is given 12 hourly or 8 hourly. We have therefore evaluated the acute and sustained (2 weeks) effects of isosorbide-5-mononitrate 40 mg given twice daily (08.00 h and 14.00 h, allowing an 18-h dose-free period) in 19 patients with stable chronic angina, using computerized exercise testing and a placebo-controlled, double-blind, randomized trial protocol. There were two phases of 2 weeks each in which patients received placebo or active isosorbide-5-mononitrate. Acute testing was performed 2 h after the first dose and chronic testing 2 h after the morning dose on Day 14. Acute testing showed an increase in exercise time from a mean (SD) of 6.7 (2.2) min to 10.1 (2.95) min (P less than 0.01) after a single dose of isosorbide-5-mononitrate 40 mg. The time to 1 mm of ST depression, and rest and peak exercise heart rates increased significantly during acute testing with isosorbide-5-mononitrate; resting and peak exercise systolic blood pressures fell significantly. Due to drop outs cross-over analysis was performed on...Continue Reading

References

Oct 1, 1986·The American Journal of Cardiology·R S KohliE B Raftery
Jul 1, 1981·The American Journal of Medicine·W S ColucciE Braunwald
Mar 1, 1984·The American Journal of Cardiology·N S KhurmiE B Raftery
Aug 1, 1984·International Journal of Cardiology·N S KhurmiE B Raftery
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Jun 27, 1983·The American Journal of Medicine·P W Armstrong, J A Moffat
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Jan 1, 1981·European Journal of Clinical Pharmacology·U Abshagen, S Spörl-Radun

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Citations

Sep 15, 1990·The American Journal of Cardiology·L O HughesE B Raftery
Oct 29, 2013·The Cochrane Database of Systematic Reviews·Jane C BallantyneGanesan Baranidharan

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