Bioavailability and pharmacokinetics of oral topotecan: a new topoisomerase I inhibitor

摘要: The results of preclinical and clinical studies indicate enhanced antineoplastic activity topotecan (SKF 104864-A) when administered as a chronic treatment. We determined the apparent bioavailability pharmacokinetics orally to 12 patients with solid tumours in two-part crossover study. oral dose 1.5 mg m-2 was drinking solution 200 ml on day 1. i.v. 30 min continuous infusion 2. calculated ratio area under curve (AUC) up last measured time point. well tolerated. revealed moderate inter-patient variation 30% +/- 7.7% (range 21-45%). maximum plasma concentration after administration (Tmax) 0.78 h (median; range 0.33-2.5). Total clearance 824 154 min-1 535-1068 min(-1)). AUC lactone ring-opened hydrolysis product (hydroxy acid) same order (0.34-1.13) (0.47-0.98) administration. illustrates significant systemic exposure drug which may enable