The Disposition of Doxorubicin on Repeated Dosing

Daniel A. Rushing, Stephen C. Piscitelli, Keith A. Rodvold, Duane A. Tewksbury

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Twelve cancer patients (aged 49–74 years) receiving doxorubicin (66 ± 8 mg/m2) as a 1‐hour intravenous infusion had serial serum samples (0–48 hours) obtained after the first and second courses of therapy. Mean number of days between courses was 24.3, and all patients had normal liver function. Patients received the same concomitant antineoplastic agents and doses in both courses. Doxorubicin and doxorubicinol concentrations were assayed by high‐performance liquid chromatography and fitted to a two‐ or three‐compartment infusion model. White blood cell and platelet toxicity were evaluated as (initial — nadir/initial)* 100. Differences in pharmacokinetic parameters were determined by a paired t test. Wide intrapatient and interpatient variability was seen between therapeutic courses. A significant decrease in the apparent volume of distribution of the central compartment (Vc = 16.6 versus 10.4 L/m2; P <.05), and a nonsignificant decrease in clearance (CL = 748 versus 658 mL/min/m2) was observed on the second course of therapy. Doxorubicinol area under the curve and elimination half‐life were similar between courses. Extensive chemotherapy‐induced changes in white blood cell and platelet counts were observed but were similar in degree for courses 1 and 2. These data suggest that higher initial doxorubicin concentrations on the second course of therapy are secondary to an alteration in distribution volume (Vc). In this subset of patients, however, these changes were not associated with an increase in hematologic toxicity. 1993 American College of Clinical Pharmacology

Original languageEnglish (US)
Pages (from-to)698-702
Number of pages5
JournalThe Journal of Clinical Pharmacology
Volume33
Issue number8
DOIs
StatePublished - Aug 1993

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Rushing, D. A., Piscitelli, S. C., Rodvold, K. A., & Tewksbury, D. A. (1993). The Disposition of Doxorubicin on Repeated Dosing. The Journal of Clinical Pharmacology, 33(8), 698-702. https://doi.org/10.1002/j.1552-4604.1993.tb05609.x