Pharmacodynamics and pharmacokinetics of a 72-hour infusion of 9-aminocamptothecin in adult cancer patients

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
C H TakimotoJ L Grem

Abstract

To investigate the pharmacokinetics and pharmacodynamics of 9-aminocamptothecin (9-AC) infused over 72 hours at doses of 5 to 74 micrograms/m2/h. 9-AC lactone and total (lactone plus carboxylate) plasma concentrations were measured in 44 patients with solid tumors using a high-performance liquid chromatography (HPLC) assay. Fifteen patients underwent extended pharmacokinetic sampling to determine the distribution and elimination kinetics of 9-AC. At steady-state, 8.7% +/- 4.7% (mean +/- SD) of the total drug circulated in plasma as the active 9-AC lactone. Clearance of 9-AC lactone was uniform (24.5 +/- 7.3 L/h/m2) over the entire dose range examined; however, total 9-AC clearance was nonlinear and increased at higher dose levels. In 15 patients treated at dose levels > or = 47 micrograms/m2/h, the volume of distribution at steady-state for 9-AC lactone was 195 +/- 114 L/m2 and for total 9-AC it was 23.6 +/- 10.6 L/m2. The elimination half-life was 4.47 +/- 0.53 hours for 9-AC lactone and 8.38 +/- 2.10 hours for total 9-AC. In pharmacodynamic studies, dose-limiting neutropenia correlated with steady-state lactone concentrations (Css) R2 = .77) and drug dose (R2 = .71). Plasma 9-AC concentrations rapidly declined to low levels f...Continue Reading

Citations

Sep 28, 1998·Cancer Chemotherapy and Pharmacology·L Iyer, M J Ratain
Jun 3, 2009·Cancer Chemotherapy and Pharmacology·Chao XuDonald E Mager
Feb 24, 2001·Annals of the New York Academy of Sciences·J W SingerS Wallace
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·V M HerbenW W ten Bokkel Huinink
Feb 24, 2001·Annals of the New York Academy of Sciences·C H Takimoto, R Thomas
Feb 24, 2001·Annals of the New York Academy of Sciences·F MuggiaH Wasserstrom
Mar 23, 2001·Anti-cancer Drugs·D F KehrerA Sparreboom
Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J de JongeA Sparreboom
Jan 1, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Howard HochsterFranco M Muggia
Oct 12, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Noriko MasubuchiRyo Atsumi
Nov 14, 1997·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M L Rothenberg

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