DRUG NAME: Carmustine

CLASSIFICATION: alkylating agent Special pediatric considerations are noted when applicable, otherwise adult provisions apply. MECHANISM OF ACTION: Carmustine is a highly lipid-soluble nitrosurea compound. Carmustine, a bifunctional alkylating agent,2 alkylates DNA and RNA, can cross-link DNA, and inhibits several enzymes by carbamoylation.1 It is cell-cycle phase nonspecific.3 Carmustine is generally not cross-resistant with other alkylating agents,4 however, cross-resistance between carmustine and lomustine has occurred.1 PHARMACOKINETICS: Table refers to intravenous (IV) dosing. Pharmacokinetic properties of the implantable carmustine-impregnated wafer have not been evaluated.5 High-dose4 is defined here as>200 mg/m2. Oral Absorption not known6 highly lipid soluble7 (e.g., enters breast milk, brain) cross blood brain barrier? passes readily1 (15-70 % of concurrent plasma concentrations) children8:>90% volume of distribution 3.25 L/kg (5.1 L/kg, high dose)9 children8: 90 L/m2 Distribution plasma protein binding 80% children8: 65-75% rapid spontaneous decomposition2; significant hepatic metabolism2,7 active metabolite(s) yes1 Metabolism inactive metabolite(s) yes6 predominately renal; respiratory 6-10%7 as CO2 urine7 60-70 % within 96 h feces1 <1% terminal half life 0.25-0.75 h, non-linear dose-related Excretion clearance 56 mL/min/kg (78 mL/min/kg, high dose)9 children8: 1,500-2,000 mL/min/m2 Adapted from standard reference4 unless specified otherwise. USES: Table refers to intravenous (IV) dosing except where specified