Etoposide

Pharmacodynamics

Etoposide belongs to the podophyllotoxin group of medicines. It is a semisynthetic derivative of podophyllotoxin, and doctors use it in the treatment of certain cancers. Podophyllotoxins work by blocking the assembly of microtubules, which stops cell division (mitosis). Etoposide slows the progress of the cell cycle at a stage just before mitosis, in the late S and G2 phases. It does not interfere with the making of nucleic acids.

Pharmacokinetics

After an intravenous dose, etoposide is cleared from the body in two phases. The first, distribution, has a half-life of about 1.5 hours. The terminal elimination half-life is between 4 and 11 hours. Total body clearance is 33 to 48 ml/min, or 16 to 36 ml/min/m2, and like the terminal half-life it does not depend on the dose across the range of 100 to 600 mg/m2. Over the same dose range, the area under the plasma concentration against time curve (AUC) and the maximum plasma concentration (Cmax) rise in direct proportion to the dose. When 100 mg/m2 is given daily for 4 to 5 days, etoposide does not build up in the plasma.

The volume of distribution at steady state is between 18 and 29 litres, or 7 to 17 L/m2.