Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Norgine Pharmaceuticals Limited, Norgine House, Widewater place, Moorhall Road, Harefield, Middlesex, UB9 6NS, UK
Pharmacotherapeutic group: Vasodilators used in cardiac diseases. organic nitrates
ATC code: C01DA08
Like all organic nitrates, isosorbide dinitrate acts as a donor of nitric oxide (NO). NO causes a relaxation of vascular smooth muscle via the stimulation of guanylyl cyclase and the subsequent increase of intracellular cyclic guanosine monophosphate (cGMP) concentration. A cGMP-dependent protein kinase is thus stimulated, with resultant alteration of the phosphorylation of various proteins in the smooth muscle cell. This eventually leads to the dephosphorylation of the light chain of myosin and the lowering of contractility.
After administration of one tablet of Isoket Retard 20 at least two peak concentrations of ISDN occurred in the plasma. The initial peak (mean 1.9 ng/ml, range 1.0 to 3.4 ng/ml) occurred during 0.5 to 2 hours and then the mean plasma concentrations declined to 1.3 ng/ml at 3 hours. The concentration then increased again to reach a major peak level (mean 6.2 ng/ml range 1.6 to 12.3 ng/ml) during 4 to 6 hours after dosing. Plasma concentrations of ISDN have been measured after administration of increasing doses in the range 20 to 100 mg as Isoket Retard 20 tablets. Means of peak concentrations of 4.2 ng/ml, 13.1 ng/ml, 20.7 ng/ml, 36.8 ng/ml and 34.9 ng/ml were measured after doses of 20mg, 40mg, 60mg, 80mg and 100mg respectively.
Gastrointestinal absorption is slower than absorption through the oral mucosa. The first pass effect is higher when given orally. Isosorbide dinitrate is metabolised to isosorbide 2-mononitrate with a half life of 2.01 h (±0.4 h) to 2.5 h and isosorbide 5-mononitrate with a half-life of 4.6 h (±0.8 h). Both metabolites are pharmacologically active.
The relative bioavailability of Isoket Retard in comparison to the non-sustained-release tablet amounts to more than 80% after oral use.
None stated.
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