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

Br J Cancer. 1996 May;73(10):1268-71. doi: 10.1038/bjc.1996.243.


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

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacokinetics
  • Biological Availability
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemistry
  • Camptothecin / metabolism
  • Camptothecin / pharmacokinetics
  • Carcinoma, Small Cell / drug therapy
  • Colonic Neoplasms / drug therapy
  • Cross-Over Studies
  • Female
  • Humans
  • Hydroxy Acids
  • Lactones
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Ovarian Neoplasms / drug therapy
  • Topoisomerase I Inhibitors*
  • Topotecan


  • Antineoplastic Agents
  • Hydroxy Acids
  • Lactones
  • Topoisomerase I Inhibitors
  • Topotecan
  • Camptothecin