Nitrates are highly effective in the prophylaxis of symptomatic and asymptomatic myocardial ischaemia. Nitrates dilate coronary arteries not only in prestenotic and poststenotic vessels, but also in eccentric lesions. The natural initiator of vascular relaxation is thought to be endothelium-derived relaxing factor (EDRF), which has both the clinical and biological characteristics of nitric oxide (NO). Organic nitrates are metabolised to NO in the muscle cell via a sulfhydryl dependent mechanism. They are therefore thought to be the physiological substitute for EDRF.
After repeated once daily administration of GenRx Isosorbide Mononitrate 60 mg Sustained Release tablets, the maximum plasma level (about 3,000 nanomol/L) of isosorbide mononitrate is achieved at about four hours. The plasma concentration remains above 1,400 to 1,500 nanomol/L for approximately ten hours, dropping to under 500 nanomol/L by the end of the dosage interval (24 hours after dose). This nitrate low period minimises the possibility of nitrate tolerances developing during prolonged treatment with GenRx Isosorbide Mononitrate 60 mg Sustained Release tablets.
Isosorbide mononitrate is less than 5% plasma protein bound. The distribution volume of isosorbide mononitrate is about 0.6 L/kg, indicating that it is mainly distributed into total body water. Elimination takes place predominantly by hydrolysis of the nitrate and conjugation in the liver. The metabolites are excreted mainly via the kidneys, with only about 2% of the dose being excreted intact.
In placebo controlled studies, isosorbide mononitrate sustained release tablets have been shown to significantly increase exercise capacity in patients with angina pectoris taking no other chronic treatment, as well as in patients taking concomitant beta-blocker therapy.
It is known that the clinical effects may be attenuated during repeated administration with nitrates in high doses and/or frequent administration. However, the pharmacokinetic characteristics of GenRx Isosorbide Mononitrate 60 mg Sustained Release tablets produce a nitrate low period following once daily dosage. No development of tolerance with respect to antianginal effect has been detected when isosorbide mononitrate sustained release tablets are given at a dose of one or two tablets (60 or 120 mg) once daily. The drug is not recommended for twice daily administration.
There is insufficient evidence to show that one halved tablet of GenRx Isosorbide Mononitrate delivers exactly half the dose of one full tablet, or whether the rate of release is the same. In vitro dissolution testing showed that dissolution was slightly faster with halved isosorbide mononitrate sustained release tablets than with whole tablets.
Very common: Headache predominates (up to 30%) necessitating withdrawal of 2 to 3 % of patients, but the incidence reduces rapidly as treatment continues .
Common: Tiredness, sleep disturbances (6%) and gastrointestinal disturbances (6%) have been reported during clinical trials with isosorbide mononitrate modified release tablets, but at a frequency no greater than for placebo. Hypotension (4 to 5%), poor appetite (2.5%), nausea (1%).
Adverse effects associated with the clinical use of the drug are as expected with all nitrate preparations. They occur mainly in the early stages of treatment.
Hypotension (4%) with symptoms such as dizziness and nausea (1%) have been reported. These symptoms generally disappear during long-term treatment.
Lotus Pharmaceuticals, Inc. Achieves Significant Milestones in the Development of Isosorbide Mononitrate Sustained Release Tablets.
Feb 18, 2008; Lotus Pharmaceuticals, Inc. (BULLETIN BOARD: LTUS) ("Lotus" or the "Company a pharmaceutical company in the People's Republic of...
Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate.(Abstract)
Aug 01, 2002; Bharani A, Ganguli A, Mathur LK, et al. Indian Heart J 2002;54:170-175. BACKGROUND: Terminalia arjuna, an Indian medicinal plant,...