Etoposide is a ligand and weak inhibitor of Cyp3A4. In spite of a molecular structure compatible with a potential for irreversible CYP-inhibition, theoretical and clinical evidence point to no significant CYP-inducing capacity. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.

Etoposide is a semisyntetic derivative of podophyllotoxin. The central tetracyclic structure carries a benzodioxole function with theoretical potential for generation of reactive carbamene, which strongly coordinates to the CYP iron atom (Fontana, 2005).

Etoposide is used alone or in combination therapy to treat lung cancer, acute non-lymphatic anemia, non-Hodgkin lymphoma, Mb Hodgkin, and testicular cancer. Administered by venous infusion, but may also be given orally. Common adverse reactions of etoposide that can be confused with an acute porphyric attack nausea, vomiting, and diarrhoea. Less common are abdominal pain and peripheral neuropathies of limited severity. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.

Metabolized in the liver by CYP 3A4 and to lesser extent by CYP 1A2 and 2E1 (Kawashiro, 1998). Molecular structure with potential for irreversible Cyp-inhibition, but findings differ: Rendic (2002) and Zhou (2007) report etoposide to be a weak inhibitor of 3A4, while Baumhakel (2001) found no clear inhibitory effect in human liver microsomes. Found to be a ligand to PXR in studies with mice (Schuetz, 2002) but not in human PXR (Sinz, 2006; Harmsen, 2009). No interactions with CYP-metabolism of other drugs are observed.

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