Pharmacokinetics of etoposide after oral and intravenous administration in patients with stomach carcinoma

Abstract

The effects of the primary tumour in situ or of gastrectomy on the bioavailability and other pharmacokinetic parameters of etoposide, after oral administration of commercially available etoposide (Vepesid®, Bristol-Myers Squibb) capsules, were studied in 8 patients with histologically proven gastric carcinoma. The dose of etoposide was 50mg. The oral bioavailability was found to be 56 ± 14%, which was similar to values reported in other studies in patients without malignancies of the gastrointestinal tract. After intravenous and oral administration, the apparent volumes of distribution were 21.5 ± 10.4 and 27.7 ± 11.1 L/m2, respectively, the mean residence times were 9.0 ± 2.6 and 10.2 ± 2.7 hours, respectively, and the elimination half-lives were 11.8 ± 5.9 and 7.8 ± 1.7 hours, respectively. These pharmacokinetic parameters were not significantly different after intravenous and oral administration. The plasma clearance of etoposide was 21.6 ± 3.2 ml/min/m2. The bioavailability of etoposide was not significantly altered (p > 0.05) by reversing the sequence of administration, nor were the apparent volume of distribution, the mean residence time or the terminal half-life of etoposide in plasma. Although the number of patients was small, it can be concluded that the pharmacokinetic parameters of etoposide are not altered in the presence of gastric cancer or gastrectomy.