Jan 1, 1990

Pharmacokinetics of chlorambucil-tertiary butyl ester, a lipophilic chlorambucil derivative that achieves and maintains high concentrations in brain

Cancer Chemotherapy and Pharmacology
N H GreigS I Rapoport

Abstract

Equimolar doses of chlorambucil (10 mg/kg) and the lipophilic chlorambucil derivative, chlorambucil-tertiary butyl ester (13 mg/kg), were given i.v. to rats. Plasma and brain concentrations of chlorambucil and its active metabolites, 3,4-dehydrochlorambucil and phenylacetic mustard, as well as of chlorambucil-tertiary butyl ester were then determined by HPLC between 2 and 240 min after drug administration. Chlorambucil demonstrated a monophasic disappearance from plasma following its administration, with a half-life of 28 min. Significant amounts of phenylacetic mustard were detected after 15 min, and this agent maintained high levels of active compounds in plasma throughout the study. Only low concentrations of chlorambucil and phenylacetic mustard were detected in brain between 2 and 120 min. Following equimolar chlorambucil-tertiary butyl ester administration, it rapidly disappeared from plasma, with a half-life of approximately 2 min, and maintained low plateau concentrations between 15 and 120 min after treatment. It was not detected thereafter, although significant amounts of chlorambucil and phenylacetic mustard were detected throughout the study. Significant amounts of chlorambucil-tertiary butyl ester entered and remai...Continue Reading

Mentioned in this Paper

chlorambucil-tertiary butyl ester
Intravenous Injections
August Rats
Brain
Neoplasms
Lympholysin
Serum Proteins
Plasma Protein Binding Capacity
High Pressure Liquid Chromatography Procedure
NSC-3088

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