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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Pharmacokinetics of chemotherapeutic agents in pregnancy: A preclinical and clinical study
Acta Obstetricia et Gynecologica Scandinavica, Volume 89, No. 10, Year 2010
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Description
Objective. To determine the impact of physiologic changes of pregnancy on pharmacokinetics of chemotherapeutic agents. Design. A preclinical and a clinical casecontrol 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. © 2010 Informa Healthcare.
Authors & Co-Authors
van Calsteren, Kristel V.
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Verbesselt, René
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Ottevanger, Nelleke P.
Netherlands, Nijmegen
Radboud University Medical Center
Halaška, Michael J.
Czech Republic, Prague
Charles University
Heyns, Liesbeth
Belgium, Leuven
Ku Leuven– University Hospital Leuven
van Bree, Rita
Belgium, Leuven
Ku Leuven– University Hospital Leuven
de Bruijn, Ernst A.
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Chai, Daniel C.
Kenya, Nairobi
National Museums of Kenya
Delforge, Michel
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Noens, Lucien A.
Belgium, Ghent
Universitair Ziekenhuis Gent
Renard, Vincent
Belgium, Ghent
Deparment of Pathology
Witteveen, Els O.
Netherlands, Utrecht
University Medical Center Utrecht
Rob, Lukáŝ
Czech Republic, Prague
Charles University
de Hoon, Jan N.J.M.
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Amant, Frédéric C.H.
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Statistics
Citations: 109
Authors: 15
Affiliations: 7
Identifiers
Doi:
10.3109/00016349.2010.512070
ISSN:
00016349
e-ISSN:
16000412
Research Areas
Cancer
Health System And Policy
Maternal And Child Health
Sexual And Reproductive Health
Study Design
Cross Sectional Study
Cohort Study
Participants Gender
Female