Pharmacokinetics of doxorubicin in pregnant women

Ryu, Rachel; Eyal, Sara; Kaplan, Henry G.; Akbarzadeh, Arezoo; Hays, Karen; Puhl, Kristin; Easterling, Thomas R.; Berg, Stacey L.; Scorsone, Kathleen A.; Feldman, Eric; Umans, Jason G.; Miodovnik, Menachem; Hébert, Mary F.

doi:10.1007/s00280-014-2406-z

Cited by 35 publications

(33 citation statements)

References 35 publications

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“…Three of these drugs are part of the antimalarial drug group (pyrimethamine [199,200], sulfadoxine [199,200], and DHA [192–194,197,198]), two are antithrombotic drugs (unfractionated heparin [113,114] and low-molecular-weight heparin [46,114–117]), one is an antibiotic (ampicillin [67,68]), and the last is an anticancer chemotherapeutic drug (doxorubicin [205,216]). The average quality score of the consistent antibiotic and antithrombotic studies tended to be higher than the quality score of the inconsistent studies from the same group (14.4 versus 11.5, p < 0.05, and 16.4 versus 15.5, p = 0.119, for the antibiotic and antithrombotic drugs, respectively).…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

et al. 2016

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BackgroundWomen are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy.Methods and FindingsSystematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown.ConclusionThis systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.

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Section: Discussionmentioning

confidence: 99%

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

et al. 2016

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“…The physiologic changes that occur during pregnancy result in altered drug disposition and response to many medications. Pregnancy alters apparent drug metabolizing enzyme activity, renal filtration, apparent renal drug transporter activity, protein binding, and volume of distribution . However, dosage adjustments based on pharmacokinetic changes during pregnancy must take into account alterations in pharmacodynamics as well as maternal, fetal, and neonatal safety .…”

Section: Physiologic Changes During Pregnancymentioning

confidence: 99%

“…There are many drug metabolizing enzymes, both phase 1 and phase 2, that have been shown to change during pregnancy . Most of the work has focused on the cytochrome P450 (CYP) enzymes, such as CYP3A, CYP2E1, CYP2D6, CYP2C9, CYP2C19, and CYP1A2; however, there are also data on uridine diphosphate‐glucuronosyltransferase 1A4 (UGT1A4) and limited data on carbonyl reductase 1 (CBR1) .…”

Section: Physiologic Changes During Pregnancymentioning

confidence: 99%

“…There are many drug metabolizing enzymes, both phase 1 and phase 2, that have been shown to change during pregnancy. [1][2][3][4][5][6][7][8] Most of the work has focused on the cytochrome P450 (CYP) enzymes, such as CYP3A, CYP2E1, CYP2D6, CYP2C9, CYP2C19, and CYP1A2; however, there are also data on uridine diphosphate-glucuronosyltransferase 1A4 (UGT1A4) and limited data on carbonyl reductase 1 (CBR1). [1][2][3][4][5][6][7][8] Some enzymes have an apparent increase in activity (e.g., CYP3A, CYP2E1, CYP2D6, CYP2C9, and UGT1A4), whereas others undergo an apparent decrease in activity (e.g., CYP1A2 and CBR1) across gestation, as depicted in Figure 1.…”

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confidence: 99%

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Pregnancy‐related pharmacokinetic changes

Tasnif

Morado

Hebert

2016

Clin Pharma and Therapeutics

107

104

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The pharmacokinetics of many drugs are altered by pregnancy. Drug distribution and protein binding are changed by pregnancy. While some drug metabolizing enzymes have an apparent increase in activity, others have an apparent decrease in activity. Not only is drug metabolism affected by pregnancy, but renal filtration is also increased. In addition, pregnancy alters the apparent activities of multiple drug transporters resulting in changes in the net renal secretion of drugs.

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“…CBR1, another important phase II enzyme, is involved in the metabolism of several compounds, such as doxorubicin, daunorubicin, vitamin E, and coenzyme Q. The activity of this enzyme is inhibited by 17β-estradiol during pregnancy (22).…”

Section: Enzymes In Food-drug Interactions In Drug Metabolismmentioning

confidence: 99%

Physiological and Pharmacokinetic Alterations and Drug-Nutrient Interactions During Pregnancy

Ede¹,

Ünal²

2017

Istanbul Med J

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During pregnancy, a large part of the body is affected by the physiological and anatomical changes that start in early pregnancy. Many of these changes significantly affect the pharmacokinetic (absorption, distribution, metabolism, and excretion) and pharmacodynamic properties of different drugs (1-3). During treatment, the use of medicines with the content of only some active ingredients is important to ensure maternal and fetal safety during pregnancy (4-6).Drug-nutritional element interactions are defined as the physicochemical, physiological, and pathophysiological relationships between a drug and nutritional element or between a drug and multiple nutritional elements, nutrients, and constituents or the nutritional status in a broader sense (6-8). Drug-nutritional element interactions can occur in four steps: extracellular bioinactivation, decrease/increase in absorption, decrease/increase in efficacy, and decrease/ increase in excretion (elimination) (7). Therefore, the fact that health professionals consider the physiological changes and the factors affecting the distribution of the drug in the body during pregnancy is important to ensure the effectiveness of pharmacotherapy. In this review article, we aimed to investigate the effects of physiological changes during pregnancy on the pharmacokinetic properties of the drug and the interactions of drugs, nutrients, and nutritional elements. Physiological Changes and Drug Metabolism in PregnancyPregnancy is a process in which many physiological differentiations occur in the cardiovascular, respiratory, excretory, gastrointestinal, and circulatory systems, which alter the interactions of nutrition, nutritional element, and drug metabolism. In summary, the rate and volume of the heart increase, lung capacity decreases, glomerular filtration rate (GFR) increases, blood volume increases, blood circulation decreases, and gastrointestinal system (GIS) motility decreases; in addition, changes, such as nausea and vomiting, occur affecting nutrition. The physiological changes associated with pregnancy are summarized in Table 1. During pregnancy, the interactions between drug metabolism and nutrition and nutritional element may be pharmaceutical, pharmacokinetic, and pharmacodynamic. The pharmaceutical interactions occur within the delivery medium, such as enteral tube or gastrointestinal lumen. This can affect the bioavailability of the drug or nutritional element (8). The pharmacokinetic interactions include the processes of absorption, distribution, metabolism, and excretion of the drug or nutritional element. The pharmacodynamic interactions include physiological changes Physiological and Pharmacokinetic Alterations and DrugNutrient Interactions During PregnancyDuring pregnancy, many physiological and metabolic alterations occur to support the requirements of the developing fetus. Alterations associated with the respiratory, cardiovascular, hematological, urinary, and gastrointestinal systems (GIS) may result in pregnancy-related disorders and may change the pharmac...

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Pharmacokinetics of doxorubicin in pregnant women

Cited by 35 publications

References 35 publications

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

Pregnancy-Associated Changes in Pharmacokinetics: A Systematic Review

Pregnancy‐related pharmacokinetic changes

Physiological and Pharmacokinetic Alterations and Drug-Nutrient Interactions During Pregnancy

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