The therapeutic benefits achieved with diltiazem hydrochloride, such as improvement of myocardial ischemia and hypotensive effect, are believed to be related to its ability to dilate vessels by inhibiting the influx of calcium ions into the smooth muscle cells of the coronary and peripheral blood vessels.
Action on myocardial ischemia:
Improving action on the balance of myocardial oxygen demand and supply: Diltiazem hydrochloride increases coronary blood flow into the myocardial ischemic region by dilating the large coronary artery and the collateral channels (dogs).
Diltiazem hydrochloride inhibits coronary artery spasms (monkeys, humans).
Diltiazem hydrochloride decreases myocardial oxygen consumption without decreasing cardiac output by decreasing the afterload and heart rate though peripheral vasodilation (dogs).
Action on myocardial protection:
Diltiazem hydrochloride maintains cardiac function and myocardial energy metabolism, and reduces the infarct size by inhibiting excess calcium ion influx into the cells under myocardial ischemia (rats).
Action on blood pressure:
Diltiazem hydrochloride lowers an elevated blood pressure gradually, although it hardly affects the normal blood pressure (rats, humans),
and it suppresses the elevation of blood pressure induced by exercise load (humans).
Diltiazem hydrochloride lowers blood pressure without decreasing the cerebral and renal blood flow (dogs, humans).
Diltiazem hydrochloride suppresses myocardial and vascular hypertrophy while lowering blood pressure (rats).
Action on sinus rhythm and cardiac conduction system:
Diltiazem hydrochloride prolongs slightly spontaneous sinus rhythm intervals and the A-H conduction time, but it does not affect the H-V conduction time (dogs, humans).
Angina pectoris, variant angina pectoris: The usefulness of HERBESSER and HERBESSER 60 in the treatment of angina pectoris was demonstrated by double blind comparative clinical trials, single blind comparative clinical trials, and open labeled clinical trials. The usefulness of the drug in the treatment of variant angina pectoris was demonstrated by open labeled clinical trials, including investigation with the Holter electrocardiogram.
Hypertension: The usefulness of HERBESSER and HERBESSER 60 in the treatment of essential hypertension was demonstrated by four double blind comparative clinical trials with a placebo, reserpine, and propranolol as the control drugs.
Pharmacokinetics: Blood concentration:
When 2 tablets of HERBESSER (60 mg of diltiazem hydrochloride) were orally administered to healthy adult men, its plasma concentration reached a maximum 3 to 5 hours after administration, and decreased thereafter with a half-life of about 4.5 hours. On daily oral administrations, the plasma concentration of diltiazem reached a steady state 2 days after the start of administration. During the long-term, repeated oral administration of 90 mg (30 mg x 3)/day of diltiazem hydrochloride to patients, its plasma concentration 2 to 4 hours after administration was about 40 ng/mL. See figure.
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In case of oral administration to healthy adult men, diltiazem hydrochloride was metabolized mainly by oxidative deamination, oxidative demethylation, deacetylation, and conjugation.