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Lookup NU author(s): Professor Herbie Newell, Professor Alan Calvert
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1 Chlorambucil (10 mg) and prednimustine (20 mg), the prednisolone ester of chlorambucil, were administered orally on separate occasions to six patients. 2 Chlorambucil was rapidly absorbed such that the parent compound was observed in the plasma 30 min after administration. 3 A preliminary comparison of chlorambucil levels following oral and intravenous administration, and after repeat oral dosage indicated that chlorambucil was well (greater than 70%) and consistently absorbed. 4 Following prednimustine no parent drug or alkylating metabolites (chlorambucil or phenyl acetic mustard) could be detected in the plasma. 5 In studies with intravenously administered chlorambucil plasma levels of the parent drug were described by a two-compartment open model with first-order kinetics. Significant levels of the cytotoxic metabolite phenyl acetic mustard were detected. 6 It is concluded that: a. the bioavailability of orally administered prednimustine is much lower than that of chlorambucil. Thus the use of prednimustine in routine combination therapy is not recommended. b. due to the lower therapeutic index of phenyl acetic mustard in experimental systems, the production of this metabolite in man may be disadvantageous. Thus research aimed at producing chlorambucil analogues, which cannot be metabolised, seems justified.
Author(s): Newell DR, Calvert AH, Harrap KR, McElwain TJ
Publication type: Article
Publication status: Published
Journal: British Journal of Clinical Pharmacology
Year: 1983
Volume: 15
Issue: 2
Pages: 253-258
Print publication date: 01/02/1983
ISSN (print): 0306-5251
ISSN (electronic): 1365-2125
URL: http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1427847&blobtype=pdf
PubMed id: 6849759
