Bicnu (Carmustine) - Description and Clinical Pharmacology

DESCRIPTION

BiCNU^® (carmustine for injection) is one of the nitrosoureas used in the treatment of certain neoplastic diseases. It is 1,3-bis (2-chloroethyl)-1-nitrosourea. It is sterile lyophilized pale yellow flakes or congealed mass with a molecular weight of 214.06. It is highly soluble in alcohol and lipids, and poorly soluble in water. BiCNU is administered by intravenous infusion after reconstitution as recommended.

The structural formula is:

BiCNU is available in 100 mg single dose vials of lyophilized material. Sterile diluent for constitution of BiCNU is co-packaged with the active drug product for use in constitution of the lyophile. The diluent is supplied in an ampule containing 3 mL of Dehydrated Alcohol Injection, USP.

CLINICAL PHARMACOLOGY

Although it is generally agreed that carmustine 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.

Intravenously administered carmustine is rapidly degraded, with no intact drug detectable after 15 minutes. However, in studies with ¹⁴C-labeled drug, prolonged levels of the isotope were detected in the plasma and tissue, probably representing radioactive fragments of the parent compound.

It is thought that the antineoplastic and toxic activities of carmustine may be due to metabolites. Approximately 60% to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory CO₂. The fate of the remainder is undetermined.

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