Idarubicin - How It Works
Clinical pharmacology details from the US FDA-approved label: how Idarubicin works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Idarubicin hydrochloride has antimitotic and cytotoxic activity through forming complexes with the DNA, inhibiting nucleic acid synthesis, inhibiting topoisomerase II activity, and producing DNA-damaging free radicals.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Idarubicin hydrochloride has antimitotic and cytotoxic activity through forming complexes with the DNA, inhibiting nucleic acid synthesis, inhibiting topoisomerase II activity, and producing DNA-damaging free radicals.
12.2 Pharmacodynamics Idarubicin hydrochloride exposure-response relationships and the time course of pharmacodynamic response have not been fully characterized.
12.3 Pharmacokinetics Idarubicin hydrochloride pharmacokinetics were determined in adult leukemia patients with normal renal and hepatic function following intravenous administration of idarubicin hydrochloride 10 to 12 mg/m 2 daily for 3 to 4 days as a single agent or combined with cytarabine.
Accumulation is predicted to be 1.7-fold for idarubicin hydrochloride and 2.3-fold for idarubicinol following multiple idarubicin hydrochloride dosing.
Distribution Idarubicin hydrochloride exhibits a rapid distributive phase with a very large volume of distribution.
Idarubicin hydrochloride is approximately 97% and idarubicinol is 94% bound to plasma proteins and the binding is concentration independent.
Concentrations of idarubicin hydrochloride and idarubicinol in nucleated blood and bone marrow cells are more than a hundred times the plasma concentrations.
Elimination Idarubicin hydrochloride mean (range) terminal half-life is 22 (4 to 48) hours when used as a single agent and 20 (7 to 38) hours when used in combination with cytarabine.
Idarubicin hydrochloride plasma clearance is twice the expected hepatic plasma flow.
Idarubicinol mean terminal half-life exceeds 45 hours; hence, its plasma levels are sustained for a period greater than 8 days.
Metabolism The idarubicin hydrochloride is primary metabolized to the active metabolite idarubicinol which has cytotoxic activity that likely contributes to the effects of idarubicin hydrochloride.
Excretion Idarubicin hydrochloride is eliminated predominately by biliary excretion and to a lesser extent by renal excretion, primarily as idarubicinol.
Specific Populations The effect of renal or hepatic impairment on idarubicin hydrochloride or idarubicinol pharmacokinetics is unknown.
Pharmacokinetics
12.3 Pharmacokinetics Idarubicin hydrochloride pharmacokinetics were determined in adult leukemia patients with normal renal and hepatic function following intravenous administration of idarubicin hydrochloride 10 to 12 mg/m 2 daily for 3 to 4 days as a single agent or combined with cytarabine. Accumulation is predicted to be 1.7-fold for idarubicin hydrochloride and 2.3-fold for idarubicinol following multiple idarubicin hydrochloride dosing. Distribution Idarubicin hydrochloride exhibits a rapid distributive phase with a very large volume of distribution. Idarubicin hydrochloride is approximately 97% and idarubicinol is 94% bound to plasma proteins and the binding is concentration independent. Concentrations of idarubicin hydrochloride and idarubicinol in nucleated blood and bone marrow cells are more than a hundred times the plasma concentrations. Elimination Idarubicin hydrochloride mean (range) terminal half-life is 22 (4 to 48) hours when used as a single agent and 20 (7 to 38) hours when used in combination with cytarabine. Idarubicin hydrochloride plasma clearance is twice the expected hepatic plasma flow. Idarubicinol mean terminal half-life exceeds 45 hours; hence, its plasma levels are sustained for a period greater than 8 days. Metabolism The idarubicin hydrochloride is primary metabolized to the active metabolite idarubicinol which has cytotoxic activity that likely contributes to the effects of idarubicin hydrochloride. Excretion Idarubicin hydrochloride is elim