title: Pharmacokinetics of doxorubicin in pregnant women.
abstract: OBJECTIVE
  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/m(2); steady-state volume of distribution (Vss), 1,132 ± 476 L/m(2); and terminal half-life (T1/2), 40.3 ± 8.9 h. The BSA-adjusted CL was significantly decreased (p < 0.01) and T1/2 was not different compared to non-pregnant women. Truncating our data to 48 h, PK parameters were: CL, 499 ± 116 ml/min/m(2); Vss, 843 ± 391 L/m(2); 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.
authors: Department of Pharmacy, University of Washington, 1959 NE Pacific Street, H-375 Health Sciences Center, Box 357630, Seattle, WA, 98195-7630, USA.
authors: Rachel J
authors: RJ
authors: Ryu
authors: Sara
authors: S
authors: Eyal
authors: Henry G
authors: HG
authors: Kaplan
authors: Arezoo
authors: A
authors: Akbarzadeh
authors: Karen
authors: K
authors: Hays
authors: Kristin
authors: K
authors: Puhl
authors: Thomas R
authors: TR
authors: Easterling
authors: Stacey L
authors: SL
authors: Berg
authors: Kathleen A
authors: KA
authors: Scorsone
authors: Eric M
authors: EM
authors: Feldman
authors: Jason G
authors: JG
authors: Umans
authors: Menachem
authors: M
authors: Miodovnik
authors: Mary F
authors: MF
authors: Hebert
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin