Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study

Acta Obstet Gynecol Scand. 2010 Oct;89(10):1338-45. doi: 10.3109/00016349.2010.512070.


Objective: To determine the impact of physiologic changes of pregnancy on pharmacokinetics of chemotherapeutic agents.

Design: A preclinical and a clinical case-control trial.

Setting: Institute of Primate Research Nairobi and collaborating hospitals in Belgium, the Netherlands and Czech Republic.

Population: Pregnant and nonpregnant women and baboons receiving chemotherapy.

Methods: Chemotherapy pharmacokinetics was compared between the pregnant and nonpregnant state. Standard-dosed chemotherapy regimens were administered in pregnant and nonpregnant baboons/women, followed by serial blood samplings. Drug plasma levels were determined using high performance liquid chromatography and atomic absorption spectrometry.

Main outcome measures: Area under the curve (AUC), maximal plasma concentration, terminal elimination half-life, clearance and distribution volume of each drug in pregnant and nonpregnant state.

Results: Intraindividual comparative pharmacokinetic data were obtained for doxorubicin and paclitaxel/platinum in three and two baboons, respectively. In the clinical trial, two patients were exposed to doxorubicin and one patient was exposed to paclitaxel/platinum during and after pregnancy. Furthermore, a pooled analysis was performed based on 16 cycles of pregnant and 11 cycles of nonpregnant women. Numbers of pregnant/nonpregnant patients were 5/2, 7/5, 4/4 and 2/2 for paclitaxel, doxorubicin, epirubicin and platinum, respectively. For all drugs tested in the preclinical and clinical study, a decreased AUC and maximal plasma concentration and an increased distribution volume and clearance were observed in pregnancy.

Conclusions: Although numbers were too small for statistical significance, pregnancy-associated physiologic alterations appear to lead to a decrease in plasma exposure of chemotherapeutic drugs. The importance of long-term follow-up of women treated with chemotherapy during pregnancy is underscored.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Bleomycin / pharmacokinetics
  • Carboplatin / pharmacokinetics
  • Case-Control Studies
  • Chromatography, High Pressure Liquid
  • Dacarbazine / pharmacokinetics
  • Doxorubicin / pharmacokinetics
  • Epirubicin / pharmacokinetics
  • Female
  • Humans
  • Models, Animal
  • Paclitaxel / pharmacokinetics
  • Papio
  • Pregnancy / blood
  • Pregnancy / metabolism*
  • Spectrophotometry, Atomic
  • Vinblastine / pharmacokinetics


  • Antineoplastic Agents
  • Bleomycin
  • Epirubicin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin
  • Carboplatin
  • Paclitaxel