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Inamrinone (Inamrinone) - Description and Clinical Pharmacology




Sterile Intravenous Solution


Inamrinone Injection USP represents a new class of cardiac inotropic agents distinct from digitalis glycosides or catecholamines. Inamrinone lactate is designated chemically as 5-Amino[3,4'-bipyridin]-6(1 H)-one 2-hydroxypropanate and has the following structure:

Inamrinone is a pale yellow crystalline compound with a molecular weight of 187.20 and a molecular formula of C10H9N3O. Each mole of lactic acid has a molecular weight of 90.08 and a empirical formula of C3H6O3. The solubilities of inamrinone at pH’s 4.1, 6.0, and 8.0 are 25, 0.9, and 0.7 mg/mL, respectively.

Inamrinone injection is a clear yellow sterile solution available in 20 mL vials for intravenous administration. Each mL contains inamrinone lactate equivalent to 5 mg of inamrinone and 0.25 mg of sodium metabisulfite added as a preservative in Water for Injection. All dosages expressed in the package insert are expressed in terms of the base, inamrinone. The pH is adjusted to between 3.2 to 4.0 with lactic acid or sodium hydroxide. The total concentration of lactic acid can vary between 5 mg and 7.5 mg.


Inamrinone is a positive inotropic agent with vasodilator activity, different in structure and mode of action from either digitalis glycosides or catecholamines.

The mechanism of its inotropic and vasodilator effects has not been fully elucidated.

With respect to its inotropic effect, experimental evidence indicates that it is not a beta-adrenergic agonist. It inhibits myocardial cyclic adenosine monophosphate (c-AMP) phosphodiesterase activity and increases cellular levels of c-AMP. Unlike digitalis, it does not inhibit sodium-potassium adenosine triphosphatase activity.

With respect to its vasodilatory activity, inamrinone reduces afterload and preload by its direct relaxant effect on vascular smooth muscle.


Following intravenous bolus (1 to 2 minutes) injection of 0.68 mg/kg to 1.2 mg/kg to normal volunteers, inamrinone had a volume of distribution of 1.2 liters/kg, and following a distributive phase half-life of about 4.6 minutes in plasma, had a mean apparent first-order terminal elimination half-life of about 3.6 hours. In patients with congestive heart failure receiving infusions of inamrinone the mean apparent first-order terminal elimination half-life was about 5.8 hours.

Inamrinone has been shown in one study to be 10% to 22% bound to human plasma protein by ultrafiltration in vitro, and in another study 35% to 49% bound by either ultrafiltration or equilibrium dialysis.

The primary route of excretion in man is via the urine as both inamrinone and several metabolites (N-glycolyl, N-acetate, O-glucuronide and N-glucuronide). In normal volunteers, approximately 63% of an oral dose of 14C-Iabelled inamrinone was excreted in the urine over a 96-hour period. In the first 8 hours, 51% of the radioactivity in the urine was inamrinone with 5% as the N-acetate, 8% as the N-glycolate, and less than 5% for each glucuronide. Approximately 18% of the administered dose was excreted in the feces in 72 hours.

In a 24-hour nonradioactive intravenous study, 10% to 40% of the dose was excreted in urine as unchanged inamrinone with the N-acetyl metabolite representing less than 2% of the dose.

In congestive heart failure patients, after a loading bolus dose, steady-state plasma levels of about 2.4 mcg/mL were able to be maintained by an infusion of 5 mcg/kg/min to 10 mcg/kg/min. In some congestive heart failure patients, with associated compromised renal and hepatic perfusion, it is possible that plasma levels of inamrinone may rise during the infusion period; therefore, in these patients, it may be necessary to monitor the hemodynamic response and/or drug level. The principal measures of patient response include cardiac index, pulmonary capillary wedge pressure, central venous pressure, and their relationship to plasma concentrations. Additionally, measurements of blood pressure, urine output, and body weight may prove useful, as may such clinical symptoms as orthopnea, dyspnea, and fatigue.


In patients with depressed myocardial function, inamrinone produces a prompt increase in cardiac output due to its inotropic and vasodilator actions.

Following a single intravenous bolus dose of inamrinone of 0.75 mg/kg to 3 mg/kg in patients with congestive heart failure, dose-related maximum increases in cardiac output occur (of about 28% at 0.75 mg/kg to about 61% at 3 mg/kg). The peak effect occurs within 10 minutes at all doses. The duration of effect depends upon dose, lasting about 1/2 hour at 0.75 mg/kg and approximately 2 hours at 3 mg/kg.

Over the same range of doses, pulmonary capillary wedge pressure and total peripheral resistance show dose-related decreases (mean maximum decreases of 29% in pulmonary capillary wedge pressure and 29% in systemic vascular resistance). At doses up to 3 mg/kg dose-related decreases in diastolic pressure (up to 13%) have been observed. Mean arterial pressure decreases (9.7%) at a dose of 3 mg/kg. The heart rate is generally unchanged.

The changes in hemodynamic parameters are maintained during continuous intravenous infusion and for several hours thereafter.

Inamrinone is effective in fully digitalized patients without causing signs of cardiac glycoside toxicity. Its inotropic effects are additive to those of digitalis. In cases of atrial flutter/fibrillation, it is possible that inamrinone may increase ventricular response rate because of its slight enhancement of A/V conduction. In these cases, prior treatment with digitalis is recommended.

Improvement in left ventricular function and relief of congestive heart failure in patients with ischemic heart disease have been observed. The improvement has occurred without inducing symptoms or electrocardiographic signs of myocardial ischemia.

At constant heart rate and blood pressure, increases in cardiac output occur without measurable increases in myocardial oxygen consumption or changes in arteriovenous oxygen difference.

Inotropic activity is maintained following repeated intravenous doses of inamrinone. Inamrinone administration produces hemodynamic and symptomatic benefits to patients not satisfactorily controlled by conventional therapy with diuretics and cardiac glycosides.

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