No data supporting CYP-affinity of mother substance or of products. Limited hepatic exposure. No observations of interference with CYP-metabolism of other drugs. Not listed as CYP-inducer or inhibitor. One report of uneventful use in AIP patient.

Chlorambucil is a nitrogen mustard analogue that is insoluble in water and contains alkylating groups common to cyscophosphamide and melphalan. Bifunctional alkylator through formation of cytotoxic ethylene- immonium radical, which bridges two DNA helix chains giving rise to interference with replication.

Chlorambucil is an alkylating agent used to treat chronic lymphatic leucemia and as palliative treatment for malignant lymphoma. Most often used in combination therapy.Given perorally. Common adverse reactions of chlorambucil that can be confused with an acute porphyric attack are Nausea, vomiting, diarrhoea. Side effects as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.

Possibly significant.

Chlorambucil is rapidly and extensively metabolized in the liver, principally to phenylacetic acid mustard, which is pharmacologically active. Phenylacetic acid mustard is formed by β-oxidation of the butyric acid side chain of chlorambucil, apparently via the dehydrogenated intermediate 3,4-dehydrochlorambucil. Chlorambucil and phenylacetic acid mustard apparently undergo spontaneous degradation in vivo, forming monohydroxy and dihydroxy derivatives. No observations of interactions with CYP-metabolism of other drugs. Not listed by Rendic (2002) as CYP-inducer or inhibitor.

Cochon et al found chlorambucil to be non-porphyrinogenic in chick embryos (Cochon, A.C. et al, 1997).

Used uneventfully in 54 year old female AIP patient with non-Hodgkin lymphoma (Davies J.H. et al, 2002).

Uneventful use reported in 1 patient with acute porphyria.