Pharmacokinetics of doxorubicin in pregnant women.

Autor: Ryu RJ; Department of Pharmacy, University of Washington, 1959 NE Pacific Street, H-375 Health Sciences Center, Box 357630, Seattle, WA, 98195-7630, USA., Eyal S, Kaplan HG, Akbarzadeh A, Hays K, Puhl K, Easterling TR, Berg SL, Scorsone KA, Feldman EM, Umans JG, Miodovnik M, Hebert MF
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2014 Apr; Vol. 73 (4), pp. 789-97. Date of Electronic Publication: 2014 Feb 15.
DOI: 10.1007/s00280-014-2406-z
Abstrakt: 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/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.
Databáze: MEDLINE
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