Ceenu Pharmacology, Pharmacokinetics, Studies, Metabolism - Lomustine

Ceenu Pharmacology, Pharmacokinetics, Studies, Metabolism - Lomustine

CLINICAL PHARMACOLOGY

Although it is generally agreed that CeeNU alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.

CeeNU may be given orally. Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m ² to 100 mg/m ² , about half of the radioactivity given was excreted in the form of degradation products within 24 hours.

The serum half-life of the metabolites ranges from 16 hours to 2 days. Tissue levels are comparable to plasma levels at 15 minutes after intravenous administration.

Because of the high lipid solubility and the relative lack of ionization at physiological pH, CeeNU crosses the blood-brain barrier quite effectively. Levels of radioactivity in the CSF are 50% or greater than those measured concurrently in plasma.