Document Detail


Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study.
MedLine Citation:
PMID:  20846067     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kristel Van Calsteren; René Verbesselt; Nelleke Ottevanger; Michael Halaska; Liesbeth Heyns; Rieta Van Bree; Ernst de Bruijn; Daniel Chai; Michel Delforge; Lucien Noens; Vincent Renard; Els Witteveen; Lukas Rob; Jan de Hoon; Frédéric Amant
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta obstetricia et gynecologica Scandinavica     Volume:  89     ISSN:  1600-0412     ISO Abbreviation:  Acta Obstet Gynecol Scand     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-17     Completed Date:  2010-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370343     Medline TA:  Acta Obstet Gynecol Scand     Country:  England    
Other Details:
Languages:  eng     Pagination:  1338-45     Citation Subset:  IM    
Affiliation:
Department of Obstetrics & Gynecology, Division of Gynecological Oncology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / blood,  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,  metabolism*
Spectrophotometry, Atomic
Vinblastine / pharmacokinetics
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 11056-06-7/Bleomycin; 23214-92-8/Doxorubicin; 33069-62-4/Paclitaxel; 41575-94-4/Carboplatin; 4342-03-4/Dacarbazine; 56420-45-2/Epirubicin; 865-21-4/Vinblastine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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