|
|
| Line 1: |
Line 1: |
| {{CMG}}
| | #REDIRECT [[Diltiazem#Pharmacology]] |
| | |
| ==General Characteristics==
| |
| <br>
| |
| <font size="4">[[Diltiazem pharmacokinetics and molecular data#Description|Description]]</font>
| |
| <br>
| |
| <br>
| |
| <font size="4">[[Diltiazem pharmacokinetics and molecular data#Pharmacokinetics and Metabolism|Pharmacokinetics and Metabolism]]</font>
| |
| <br>
| |
| <br>
| |
| <font size="4">[[Diltiazem pharmacokinetics and molecular data#Hemodynamic and Electrophysiologic Effects|Hemodynamic and Electrophysiologic Effects]]</font>
| |
| <br>
| |
| <br>
| |
| -------
| |
| <br>
| |
| ===Description===
| |
| | |
| Diltiazem hydrochloride is a calcium ion influx inhibitor (slow channel blocker or calcium antagonist). Chemically, Diltiazem hydrochloride is 1,5 - Benzothiazepin - 4(5H)one,3 - (acetyloxy) - 5 - [2 - (dimethylamino)ethyl] - 2,3 - dihydro - 2 - (4 - methoxyphenyl) - ,monohydrochloride,(+) - cis - . The structural formula is:
| |
| | |
| C22H26N2O4S•HCl M.W. 450.99
| |
| | |
| Diltiazem hydrochloride is a white to off-white crystalline powder with a bitter taste. It is soluble in water, [[methanol]], and [[chloroform]].
| |
| | |
| Each tablet for oral administration contains 30 mg, 60 mg, 90 mg, or 120 mg of Diltiazem hydrochloride. Each tablet also contains the following inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, povidone, titanium dioxide and FD&C Yellow #6 aluminum lake.
| |
| | |
| Diltiazem Hydrochloride Tablets meet USP Dissolution Test 1.
| |
| | |
| ''[[Diltiazem pharmacokinetics and molecular data#General Characteristics|Return to top]]''
| |
| <br>
| |
| ===Pharmacokinetics and Metabolism===
| |
| | |
| Diltiazem is well absorbed from the gastrointestinal tract and is subject to an extensive first-pass effect, giving an absolute bioavailability (compared to intravenous dosing) of about 40%. Diltiazem undergoes extensive hepatic metabolism in which 2% to 4% of the unchanged drug appears in the urine.
| |
| | |
| In vitro binding studies show Diltiazem is 70% to 80% bound to plasma proteins. Competitive in vitro ligand binding studies have also shown Diltiazem binding is not altered by therapeutic concentrations of [[digoxin]], [[hydrochlorothiazide]], [[phenylbutazone]], [[propranolol]], [[salicylic acid]], or [[warfarin]]. The plasma elimination half-life following single or multiple drug administration is approximately 3.0 to 4.5 hours. Desacetyl Diltiazem is also present in the plasma at levels of 10% to 20% of the parent drug and is 25% to 50% as potent as a coronary vasodilator as Diltiazem.
| |
| | |
| Minimum therapeutic plasma levels of Diltiazem appear to be in the range of 50-200 ng/mL. There is a departure from linearity when dose strengths are increased. A study that compared patients with normal hepatic function to patients with cirrhosis found an increase in half-life and a 69% increase in AUC (area-under-the plasma concentration vs time curve) in the hepatically impaired patients. A single study in nine patients with severely impaired renal function showed no difference in the pharmacokinetic profile of Diltiazem as compared to patients with normal renal function.
| |
| | |
| Single oral doses of 30 to 120 mg of Diltiazem tablets result in detectable plasma levels within 30 to 60 minutes and peak plasma levels 2 to 4 hours after drug administration. As the dose of Diltiazem tablets is increased from a daily dose of 120 mg (30 mg q.i.d.) to 240 mg (60 mg q.i.d.) daily, there is an increase in area-under-the-curve of 2.3 times. When the dose is increased from 240 mg to 360 mg daily, there is an increase in area-under-the-curve of 1.8 times.
| |
| | |
| ''[[Diltiazem pharmacokinetics and molecular data#General Characteristics|Return to top]]''
| |
| <br>
| |
| | |
| ===Hemodynamic and Electrophysiologic Effects===
| |
| | |
| Like other calcium antagonists, Diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations. In the intact animal, prolongation of the AH interval can be seen at higher doses.
| |
| | |
| In man, Diltiazem prevents spontaneous and ergonovine-provoked coronary artery spasm. It causes a decrease in peripheral vascular resistance and a modest fall in blood pressure and, in exercise tolerance studies in patients with ischemic heart disease, reduces the heart rate-blood pressure product for any given work load. Studies to date, primarily in patients with good ventricular function, have not revealed evidence of a negative inotropic effect; cardiac output, ejection fraction, and left ventricular end diastolic pressure have not been affected. There are as yet few data on the interaction of Diltiazem and beta-blockers. Resting heart rate is usually unchanged or slightly reduced by Diltiazem.
| |
| | |
| Intravenous Diltiazem hydrochloride in doses of 20 mg prolongs AH conduction time and [[AV node]] functional and effective refractory periods approximately 20%. In a study involving single oral doses of 300 mg of Diltiazem hydrochloride in six normal volunteers, the average maximum PR prolongation was 14% with no instances of greater than [[first-degree AV block]]. Diltiazem-associated prolongation of the [[AH interval]] is not more pronounced in patients with [[first-degree heart block]]. In patients with [[sick sinus syndrome]], Diltiazem significantly prolongs sinus cycle length (up to 50% in some cases).
| |
| | |
| Chronic oral administration of Diltiazem hydrochloride in doses of up to 240 mg/day has resulted in small increases in [[PR interval]], but has not usually produced abnormal prolongation.
| |
| | |
| ''[[Diltiazem pharmacokinetics and molecular data#General Characteristics|Return to top]]''
| |
| <br>
| |
| | |
| | |
| | |
| {{FDA}}
| |
| | |
| | |
| | |
| [[Category:Drugs]]
| |