Pharmacokinetics in pregnancy

Anger, G; Costantine, Maged M.; Piquette-Miller, Micheline

doi:10.1016/b978-0-12-382032-7.10004-9

Cited by 6 publications

(12 citation statements)

References 63 publications

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“…The pregnant woman has been called “the last true therapeutic orphan.” Indeed, pregnant women (and women of child‐bearing potential) have historically been excluded from clinical trials because of the well‐intentioned attempt to protect the vulnerable fetus . Unfortunately, an unintended consequence has been an information gap that makes prescribing drugs for pregnant women with preexisting illnesses or new‐onset disorders difficult and potentially dangerous for both the mother and the fetus . In the absence of knowledge regarding changes in the pharmacokinetics of a drug produced by the physiological changes of pregnancy, healthcare professionals often prescribe a standard adult dose for pregnant women.…”

Section: The Last True Therapeutic Orphanmentioning

confidence: 99%

“…A number of physiological changes occur during pregnancy that affect the pharmacokinetics of drugs. Total body weight increases, due to a substantial (6 to 8 L) increase in the volume of water found within the intravascular and the extravascular fluid spaces, which leads to a significant increase in the volume of distribution of hydrophilic drugs, and an increase in body fat, which increases the volume of distribution of lipophilic drugs . These increases in volume of distribution are likely to decrease peak concentrations and increase the elimination half‐life of drugs.…”

Section: Physiological Changes In Pregnancymentioning

confidence: 99%

“…Cardiac output increases by ∼50% early in pregnancy and the resulting changes in regional blood flow can affect both the distribution and elimination of drugs . Among the most important of these effects is the 50% to 80% increase in effective renal plasma flow that increases glomerular filtration rate and the clearance of drugs eliminated by the kidneys . Another potentially important consequence of the increased cardiac output is the increase in hepatic blood flow, which affects the clearance of drugs with high hepatic extraction ratios .…”

Section: Physiological Changes In Pregnancymentioning

confidence: 99%

“…2 Unfortunately, an unintended consequence has been an information gap that makes prescribing drugs for pregnant women with preexisting illnesses or new-onset disorders difficult and potentially dangerous for both the mother and the fetus. 1,2 In the absence of knowledge regarding changes in the pharmacokinetics of a drug produced by the physiological changes of pregnancy, healthcare professionals often prescribe a standard adult dose for pregnant women. The resulting plasma drug concentrations may be subtherapeutic if its elimination clearance is increased in pregnancy or supratherapeutic if the elimination clearance is decreased.…”

Section: The Last True Therapeutic Orphanmentioning

confidence: 99%

“…Total body weight increases, due to a substantial (6 to 8 L) increase in the volume of water found within the intravascular and the extravascular fluid spaces, which leads to a significant increase in the volume of distribution of hydrophilic drugs, and an increase in body fat, which increases the volume of distribution of lipophilic drugs. 1,2 These increases in volume of distribution are likely to decrease peak concentrations and increase the elimination half-life of drugs. Cardiac output increases by 50% early in pregnancy and the resulting changes in regional blood flow can affect both the distribution and elimination of drugs.…”

Section: Physiological Changes In Pregnancymentioning

confidence: 99%

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Rationale and design for an investigation to optimize selective serotonin reuptake inhibitor treatment for pregnant women with depression

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The physiological changes of pregnancy can affect the pharmacokinetics of a drug, thereby affecting its dose requirements. Because pharmacokinetic (PK) studies in pregnant women have rarely been conducted, evidence-based dosing adjustments are seldom available. In particular, despite the fact that the use of antidepressants has become increasingly common, pregnancy-associated PK changes of the selective serotonin reuptake inhibitors (SSRIs) are largely unknown.

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Section: The Last True Therapeutic Orphanmentioning

confidence: 99%

Section: Physiological Changes In Pregnancymentioning

confidence: 99%

Section: Physiological Changes In Pregnancymentioning

confidence: 99%

Section: The Last True Therapeutic Orphanmentioning

confidence: 99%

Section: Physiological Changes In Pregnancymentioning

confidence: 99%

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Rationale and design for an investigation to optimize selective serotonin reuptake inhibitor treatment for pregnant women with depression

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Regulation of Drug Transport Proteins—From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium

Brouwer

Evers

Hayden

et al. 2022

Clin Pharma and Therapeutics

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Membrane transport proteins are involved in the absorption, disposition, efficacy, and/or toxicity of many drugs. Numerous mechanisms (e.g., nuclear receptors, epigenetic gene regulation, microRNAs, alternative splicing, post-translational modifications, and trafficking) regulate transport protein levels, localization, and function. Various factors associated with disease, medications, and dietary constituents, for example, may alter the regulation and activity of transport proteins in the intestine, liver, kidneys, brain, lungs, placenta, and other important sites, such as tumor tissue. This white paper reviews key mechanisms and regulatory factors that alter the function of clinically relevant transport proteins involved in drug disposition. Current considerations with in vitro and in vivo models that are used to investigate transporter regulation are discussed, including strengths, limitations, and the inherent challenges in predicting the impact of changes due to regulation of one transporter on compensatory pathways and overall drug disposition. In addition, translation and scaling of in vitro observations to in vivo outcomes are considered. The importance of incorporating altered transporter regulation in modeling and simulation approaches to predict the clinical impact on drug disposition is also discussed. Regulation of transporters is highly complex and, therefore, identification of knowledge gaps will aid in directing future research to expand our understanding of clinically relevant molecular mechanisms of transporter regulation. This information is critical to the development of tools and approaches to improve therapeutic outcomes by predicting more accurately the impact of regulation-mediated changes in transporter function on drug disposition and response.Transport proteins of the solute carrier (SLC) and ATP-binding cassette (ABC) superfamilies are widely recognized as key determinants of the absorption, distribution, and excretion of many endogenous compounds and xenobiotics, including drugs, bile acids, hormones, and nutrients, which may thereby directly or indirectly impact medication efficacy and/or safety. Not surprisingly, intersubject variability in drug response due to transporters has been attributed to altered transporter function in organs, such as the intestine, liver, and kidneys. 1,2 Mechanisms of alterations in drug transporter activity have focused primarily on (i) differences in gene expression and/ or protein abundance due to genetic polymorphisms; and (ii) drug-drug interactions (DDIs) predominantly involving direct

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The impact of pregnancy on biologic therapies for the treatment of inflammatory bowel disease

Picardo

Seow

2020

Best Practice & Research Clinical Gastroenterology

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Pharmacokinetics in pregnancy

Cited by 6 publications

References 63 publications

Rationale and design for an investigation to optimize selective serotonin reuptake inhibitor treatment for pregnant women with depression

Rationale and design for an investigation to optimize selective serotonin reuptake inhibitor treatment for pregnant women with depression

Regulation of Drug Transport Proteins—From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium

The impact of pregnancy on biologic therapies for the treatment of inflammatory bowel disease

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