The effect of dose on the bioavailability of oral etoposide

The bioavailability of orally administered etoposide varies considerably. The effect of dose on bioavailability has not previously been investigated. In this study six patients were each treated with oral etoposide at doses of 200, 400, and 600 mg, and the pharmacokinetics determined. Each patient acted as his own control. The area under the plasma concentration-time curve (AUC) was proportionately greatest at the lowest dose. Doubling the dose from 200 mg to 400 mg increased AUC by only 50%, and a further increase of only 2.2% occurred at a dose of 600 mg. These data show nonlinear bioavailability of etoposide within the range in clinical use and may explain the variable results of reported studies. The data may have important implications for chemotherapy regimens with oral etoposide.