Ceenu (Lomustine / Lomustine / Lomustine) - Description and Clinical Pharmacology

DESCRIPTION

CeeNU^® (lomustine)(CCNU) is one of the nitrosoureas used in the treatment of certain neoplasticdiseases. It is 1-(2-chloro-ethyl)-3-cyclohexyl-1-nitrosourea. It is a yellowpowder with the empirical formula of C₉H₁₆ClN₃O₂ anda molecular weight of 233.71. CeeNU is soluble in 10% ethanol (0.05 mg permL) and in absolute alcohol (70 mg per mL). CeeNU is relatively insolublein water (<0.05 mg per mL).

It is relatively unionizedat a physiological pH.

Inactive ingredients in CeeNUCapsules are magnesium stearate and mannitol.

Thestructural formula is:

CeeNU is available in10 mg, 40 mg, and 100 mg capsules for oral administration.

CLINICAL PHARMACOLOGY

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

CeeNUmay be given orally. Following oral administration of radioactive CeeNU atdoses ranging from 30 mg/m² to 100 mg/m²,about half of the radioactivity given was excreted in the urine in the formof degradation products within 24 hours.

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

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