Use of etoposide in patients with organ dysfunction: pharmacokinetic and pharmacodynamic considerations

Etoposide is a podophyllotoxin deriverative with activity against a wide variety of malignancies. It is also used in many clinical conditions in which renal or hepatic function is impaired. To establish a basis for making initial dose adjustments in patients with renal or hepatic dysfunction, the clinical pharmacology (e.g., absorption, distribution, protein binding, metabolism, and elimination) of etoposide is presented. Studies of the use of etoposide in patients with renal or hepatic dysfunction are summarized. The importance of protein binding to etoposide disposition, especially in patients with hepatic dysfunction is discussed. Pharmacodynamics refers to the relationship between drug concentration at the site of action (receptor) and pharmacologic response (toxicity or efficacy). The pharmacodynamics of etoposide has been studied in only a few patients with renal and (or) hepatic dysfunction and must be studied in larger populations before definitive dosing guidelines can be recommended. However, some general initial dosing recommendations for the use of etoposide in patients with renal and hepatic dysfunction are presented.