Oral topotecan: bioavailability and effect of food co-administration

The aims of the study were twofold: (1) to evaluate the effect of food on t he relative oral bioavailability of topotecan gelatin capsules in patients with solid tumours, and (2) to determine the absolute bioavailability of or al topotecan with reference to the intravenous (i.v.) formulation. The stud y had a randomized two-period cross-over design. On day 1 of the first trea tment course patients were administered 2.3 mg m(-2) day(-1) of oral topote can with or without a high-fat breakfast. They crossed over to receive the alternate regimen on day 2. In the second course (3 weeks later) fasted pat ients received topotecan orally (2.3 mg m(-2) day(-1)) or i.v. (1.5 mg m(-3 ) day). They crossed over to receive the alternate regimen on day 2. On day s 3-5 of both treatment courses patients received oral topotecan, Plasma ph armacokinetics were performed on days 1 and 2 of the first and second cours e using a high-performance liquid chromatographic assay. Eighteen patients were enrolled in the study. The ratio of the area under the curve to infini ty during fasted and high-fat treatment was 0.93 +/- 0.23 (90% confidence i nterval (CI) 0.83-1.03). Maximal plasma concentrations of topotecan were si milar after ingestion of the capsules with (10.6 +/- 4.4 ng ml(-1)) or with out food (9.2 +/- 4.1 ng ml(-1)) (P = 0.130). The lime needed to reach maxi mal plasma levels was significantly prolonged after food intake (median 3.1 h, range 2.8-6.1) compared to fasted conditions (2.0 h, range 1.1-8.1) (P = 0.013). The absolute bioavailability of topotecan averaged 42 +/- 13% (90 % CI 37- 47%). The apparent terminal half-life was significantly longer aft er administration of oral topotecan (3.9 +/- 1.0 h) than after i.v. adminis tration (2.7 +/- 0.4 h) (P < 0.001). Topotecan demonstrates suitable bioava ilability for oral treatment. Go-administration of the topotecan gelatin ca psules with a high-fat breakfast leads to a small decrease in absorption ra te but does not affect the extent of absorption.