Pharmacokinetic study of intravenous and oral idarubicin in cancer patients.

Idarubicin (4-demethoxydaunorubicin) is a new anthracycline analogue which lacks the methoxyl group at the C-4 position of the aglycone moiety. The present study was undertaken to investigate the pharmacokinetics and bioavailability of idarubicin in man. The drug was administered at 3-week intervals to six patients by both intravenous and oral routes. Doses used were 13-15 mg/m2 intravenous and 45 mg/m2 p.o. Plasma levels of unchanged idarubicin and of its metabolite idarubicinal were assayed by high performance liquid chromatography (HPLC). After intravenous administration the plasma levels of the unchanged drug declined very rapidly reaching the sensitivity limits of the analytical method (1-2 ng/ml) 24 h after dosing. Plasma levels of idarubicinal reached a peak of about 10 ng/ml within two hours then decreased very slowly with a plasma t1/2 of about 2.5 days. After the oral dose of 45 mg/m2, the plasma level patterns of both parent compound and the idarubicinal were roughly similar to those after 15 mg/m2 intravenous except for the obvious difference linked to the absorption of idarubicin. The absorption of oral idarubicin was rapid and, in terms of area under curve of the metabolite, the availability after oral administration can be estimated as about 30% of the dose. The urine findings reflected the plasma situation. The metabolite levels were much higher and longer lasting than those of the parent compound. Urinary recovery after intravenous (16% of the dose in four days) and oral administration (approximately 5% of the dose) confirmed the 30% absorption estimated on the basis of plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)