Title: Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study
Authors: Van Calsteren, Kristel ×
Verbesselt, René
Ottevanger, Nelleke
Halaska, Michael
Heyns, Liesbeth
Van Bree, Rieta
de Bruijn, Ernst
Chai, Daniel
Delforge, Michel
Noens, Lucien
Renard, Vincent
Witteveen, Els
de Hoon, Jan
Amant, Frédéric #
Issue Date: Oct-2010
Publisher: Munksgaard
Series Title: Acta Obstetricia et Gynecologica Scandinavica vol:89 issue:10 pages:1338-45
Abstract: 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.
ISSN: 0001-6349
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Pharmacology Centre (-)
Gynaecological Oncology
Laboratory of Experimental Oncology
Hematology Section (-)
Department of Oncology - miscellaneous
× corresponding author
# (joint) last author

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