Prophylactic Therapy of Angina Pectoris With Organic Nitrates: Relationship of Drug Efficacy and Clinical Experimental Design

Stipe, A. Allan; Fink, G

doi:10.1002/j.1552-4604.1973.tb00264.x

Cited by 13 publications

(3 citation statements)

References 43 publications

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“…It has been suggested (Needleman, 1970) that, as orally administered GTN undergoes such an extensive first pass metabolism in the liver, thereapeutic levels in the plasma are never achieved. This is supported by some clinical studies (Stipe & Fink, 1973), but other workers reported that sustained release oral preparations were beneficial to patients suffering from angina (Winsor & Berger, 1975). In the present study, oral administration of GTN resulted in low bioavailability, less than 5% of the dose apparently being absorbed systemically.…”

Section: Resultssupporting

confidence: 82%

“…Animals received a single intravenous dose (0.75 mg/kg) of GTN. (Stipe & Fink, 1973), but other workers reported that sustained release oral preparations were beneficial to patients suffering from angina (Winsor & Berger, 1975). In the present study, oral administration of GTN resulted in low bioavailability, less than 5% of the dose apparently being absorbed systemically.…”

Section: Discussioncontrasting

confidence: 41%

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Elimination of Glyceryl Trinitrate: Effects of Sex, Age, Species and Route of Administration

Ioannides

Parke

Taylor

1982

British J Pharmacology

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Orally administered glyceryl trinitrate to rats undergoes extensive first pass metabolism leading to low bioavailability. Sex differences in the plasma elimination of glyceryl trinitrate were seen in the rat, the female exhibiting the longer plasma half‐life. No sex differences in this respect were detected in the rabbit. The plasma half‐life of glyceryl trinitrate was longer and the volume of distribution larger, in older animals. The plasma elimination of glyceryl trinitrate was different in various animal species. There was a good correlation between plasma half‐life and animal bodyweight.

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Section: Resultssupporting

confidence: 82%

Section: Discussioncontrasting

confidence: 41%

Elimination of Glyceryl Trinitrate: Effects of Sex, Age, Species and Route of Administration

Ioannides

Parke

Taylor

1982

British J Pharmacology

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“…M ost previous drug studies on PST w ere neither correctly designed nor placebo controlled (13). It is well know n th at controlled trials have less frequent positive results than poorly designed trials (28). T he only study whose design is relevant com pared suloctidil to nothing (5).…”

Section: Discussionmentioning

confidence: 99%

Drugs Effect on Platelet Survival Time: Comparison of Two Pyrimido-Pyrimidine Derivatives in Patients with Aortic or Mitral Replacement

Schbath

Mathy

et al. 1984

Thromb Haemost

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SummaryA prospective randomized trial of the effects of 2 antiplatelet aggregating drugs, dipyridamole (375 mg/d), a related substance RA 233 (1500 mg/d) and placebo, concomitantly with oral anticoagulants, was carried out in patients with prior valvular replacement. The study was aimed to determine effect on platelet survival time (PST) of these 2 agents. The trial sample consisted of 40 males and 15 females aged 40–70 years (average 53 years). 32 received Björk-Shiley valve in aortic position; 23 underwent mitral valve replacement: 3 with Cooley-Cutter, 11 with Lillehei- Kaster 500 and 9 with Starr-Edwards 6120 prostheses; 28 patients had aortic stenosis, 21 aortic insufficiency. All the PST measured after 3 months of treatment were within normal ranges and not different between placebo, dipyridamole or RA 233 treated subjects: averages in days were, respectively, 7.49, 7.11 and 6.88. The present study did not support the claim that modem valve prosthesis could lead to a shortened PST.

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Short and long-acting oral nitrates for stable angina pectoris

Thadani

Lipicky

1994

Cardiovasc Drug Ther

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Nitroglycerin (NTG) spray and sublingual tablets rapidly relieve an established attack of angina, and their infrequent use is not associated with the development of tolerance. Although, following a suitable nitrate-free interval, the first dose of oral, long-acting nitrates produces significant hemodynamic effects, increases angina free walking, and decreases exercise-induced ischemia, during continued long-term therapy tolerance limits their usefulness. Appropriate dosing regimens of controlled-release formulations of isosorbide dinitrate (ISDN) and controlled-release NTG during long-term therapy have not been established. Use of immediate-release formulation of 15-120 mg of ISDN in a qid regimen lead to a marked reduction in the size and duration of antianginal effects compared to the initial dose. Asymmetric tid therapy with 30 mg of ISDN (7 a.m., 1 p.m., and 6 p.m.) is also associated with the development of partial tolerance and appears to provide antianginal prophylaxis for only a period of 6 hours each day. Asymmetric bid therapy with ISDN at 7 a.m. and noon may give sustained effect but is supported by only a single, small study that did not examine effectiveness after the noon dose in long-term use. Isosorbide-5-mononitrate (IS-5-MN) has been the subject of more recent studies than other nitrates because of attempts to bring a number of products into the U.S. market. IS-5-MN in qid, tid, and standard bid (8 a.m. and 8 p.m.) dosing regimens produce tolerance. Asymmetric regimens of immediate-release IS-5-MN (10 and 20 mg) given bid (once in the morning and again 7 hours later) decrease the development of tolerance compared to symmetric regimens and produce an increased exercise duration after each dose of the day; the 20 mg bid dosing is more effective. Similarly, once-daily 120 and 240 mg controlled-release IS-5-MN does not produce tolerance and gives a sustained increase in daytime exercise duration. Both asymmetric bid immediate-release and once-daily controlled-release IS-5-MN preparations do not produce deterioration in exercise performance prior to the administration of the medication in the morning (i.e., no zero-hour effect). Further studies are needed to establish useful dosing regimens for ISDN, for controlled-release ISDN, and for controlled-release nitroglycerin. None of the dosing regimens of any oral, long-acting nitrate (including IS-5-MN) provide 24 hour antianginal and antiischemic effects.(ABSTRACT TRUNCATED AT 400 WORDS)

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Prophylactic Therapy of Angina Pectoris With Organic Nitrates: Relationship of Drug Efficacy and Clinical Experimental Design

Cited by 13 publications

References 43 publications

Elimination of Glyceryl Trinitrate: Effects of Sex, Age, Species and Route of Administration

Elimination of Glyceryl Trinitrate: Effects of Sex, Age, Species and Route of Administration

Drugs Effect on Platelet Survival Time: Comparison of Two Pyrimido-Pyrimidine Derivatives in Patients with Aortic or Mitral Replacement

Short and long-acting oral nitrates for stable angina pectoris

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