| Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study. | |
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MedLine Citation:
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PMID: 20846067 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Acta obstetricia et gynecologica Scandinavica Volume: 89 ISSN: 1600-0412 ISO Abbreviation: Acta Obstet Gynecol Scand Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-17 Completed Date: 2010-09-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370343 Medline TA: Acta Obstet Gynecol Scand Country: England |
Other Details:
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Languages: eng Pagination: 1338-45 Citation Subset: IM |
Affiliation:
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Department of Obstetrics & Gynecology, Division of Gynecological Oncology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. |
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
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