Pharmacokinetics of doxorubicin in pregnant women

Rachel J. Ryu, Sara Eyal, Henry G. Kaplan, Arezoo Akbarzadeh, Karen Hays, Kristin Puhl, Thomas R. Easterling, Stacey L. Berg, Kathleen A. Scorsone, Eric M. Feldman, Jason G. Umans, Menachem Miodovnik, Mary F. Hebert*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Purpose: Our objective was to evaluate the pharmacokinetics (PK) of doxorubicin during pregnancy compared to previously published data from non-pregnant subjects. Methods: During mid- to late-pregnancy, serial blood and urine samples were collected over 72 h from seven women treated with doxorubicin for malignancies. PK parameters were estimated using non-compartmental techniques. Pregnancy parameters were compared to those previously reported non-pregnant subjects. Results: During pregnancy, mean (±SD) doxorubicin PK parameters utilizing 72 h sampling were: clearance (CL), 412 ± 80 mL/min/m2; steady-state volume of distribution (Vss), 1,132 ± 476 L/m2; and terminal half-life (T1/2), 40.3 ± 8.9 h. The BSA-adjusted CL was significantly decreased (p < 0.01) and T 1/2 was not different compared to non-pregnant women. Truncating our data to 48 h, PK parameters were: CL, 499 ± 116 ml/min/m2; Vss, 843 ± 391 L/m2; and T1/2, 24.8 ± 5.9 h. The BSA-adjusted CL in pregnancy compared to non-pregnant data was significantly decreased in 2 of 3 non-pregnant studies (p < 0.05, < 0.05, NS). Vss and T1/2 were not significantly different. Conclusions: In pregnant subjects, we observed significantly lower doxorubicin CL in our 72 h and most of our 48 h sampling comparisons with previously reported non-pregnant subjects. However, the parameters were within the range previously reported in smaller studies. At this time, we cannot recommend alternate dosage strategies for pregnant women. Further research is needed to understand the mechanism of doxorubicin pharmacokinetic changes during pregnancy and optimize care for pregnant women.

Original languageAmerican English
Pages (from-to)789-797
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume73
Issue number4
DOIs
StatePublished - Apr 2014

Bibliographical note

Funding Information:
Acknowledgments S. eyal, t. r. easterling, S. l. Berg, K. a. Scorsone and M. F. Hebert: grant number U10HD047892 from the eunice Kennedy Shriver national Institute of Child Health & Human Development, national Institutes of Health and national Center for research resources grant numbers M01rr00037 and rr023256. J.g. Umans and M. Miodovnik: grant number U10HD047891 from the eunice Kennedy Shriver national Institute of Child Health & Human Development, national Institutes of Health. the content is solely the responsibility of the authors and does not necessarily represent the official views of the eunice Kennedy Shriver national Institute of Child Health & Human Development or the national Institutes of Health.

Keywords

  • Adriamycin
  • Doxorubicin
  • Doxorubicinol
  • Pharmacokinetics
  • Pregnancy

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