Pharmacokinetics, metabolism and elimination of itanoxone in humans.

The pharmacokinetics, metabolism and elimination of Itanoxone was studied after a single oral administration of the carbon-14-labelled drug (500 mg) in four male volunteers. The drug was absorbed fairly rapidly with a mean peak plasma level of 10.3 +/- 1.3 micrograms/ml between 3 and 4 hours after dosing. The pharmacokinetics can be described by a two-compartment open model with the central compartment consisting of the extracellular fluid. The mean elimination half-life was 19.4 +/- 8.5 hours. Two metabolites as well as unchanged Itanoxone were detected in plasma. Approximately 37% of the radioactivity was excreted over a five-day period in the urine and 50% in the faeces. There were only traces of free metabolites in the urine as the rest of the radioactive metabolites were associated with glucuronide conjugates. These conjugates consisted of Itanoxone and up to six metabolites. Five of these metabolites have been tentatively identified by comparison of their chromatographic properties by TLC and HPLC with a number of reference compounds. After repeated administration of Itanoxone (250 mg b.i.d.) the maximum level at steady state was about 7 micrograms/ml and the minimum level, 0.6 micrograms/ml. The mean area under the plasma level time curve was 35% higher than in the single dose study after correction for dose.