An overview of the clinical pharmacology of topotecan.

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Dennis MJ, Beijnen JH, Grochow LB, van Warmerdam LJ

An overview of the clinical pharmacology of topotecan.

Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-12-S5-18.

PubMed ID

9122737 [ View in PubMed

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Abstract

Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a topoisomerase I inhibitor, is a semisynthetic camptothecin that has been structurally modified for increased water solubility. The closed lactone ring predominates at acidic pH, but the reverse reaction of the parent into the metabolite predominates at physiologic pH. The pharmacokinetic profile of topotecan is usually characterized by a two-compartment model and is linear in the dose range of 0.5 to 3.5 mg/m2. Following intravenous administration for 5 days at doses of 0.5 to 1.5 mg/m2/d as a 30-minute infusion, topotecan has a volume of distribution of approximately 130 L. Mean plasma clearance for topotecan (total) was approximately 1,000 mL/min with a plasma half-life of 2 to 3 hours. Renal clearance is an important determinant of topotecan elimination, with approximately 30% of the dose excreted in the urine. In three phase I studies in which the schedule of five daily doses every 21 or 28 days was investigated, all found 1.5 mg/m2/d to be the maximum tolerated dose. Neutropenia (reversible and noncumulative over time) was the major dose-limiting toxicity; fevers and infections were infrequently reported. The magnitude of topotecan exposure was correlated to the observed myelosuppression.

DrugBank Data that Cites this Article

Drugs

Topotecan

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Topotecan	DNA topoisomerase 1	Protein	Humans	Yes	Inhibitor	Details