Preclinical studies indicate enhanced antitumor activity of 9-amino-20(S)-camptothecin (9-AC) when it is administered in a manner that provides prolonged systemic exposure. In view of this observation, the pharmacokinetics and oral bioavailability of 9-AC polyethylene glycol 1000 capsules were evaluated in 12 patients with solid tumors. Patients were randomized to receive either 1.5 mg/m2 9-AC p.o. on day 1 and 1.0 mg/m2 9-AC i.v. on day 8 or vice versa. Serial plasma samples were collected up to 55 h after dosing and analyzed for 9-AC by liquid chromatography. Plasma concentrations of the lactone and carboxylate forms of 9-AC rapidly reached an equilibrium, with the active lactone accounting for < 10% of total drug at the terminal disposition phase. The drug demonstrated peak levels at 1.2 h and an overall bioavailability of 48.6+/-17.6% (range, 24.5-80.4%), indicating significant systemic exposure to the drug, which may enable chronic oral treatment.