Physiologic Changes During Pregnancy and Impact on Small‐Molecule Drugs, Biologic (Monoclonal Antibody) Disposition, and Response

Abstract

Pregnancy is a unique physiological state that results in many changes in bodily function, including cellular, metabolic, and hormonal changes. These changes can have a significant impact on the way small‐molecule drugs and monoclonal antibodies (biologics) function and are metabolized, including efficacy, safety, potency, and adverse effects. In this article, we review the various physiologic changes that occur during pregnancy and their effects on drug and biologic metabolism, including changes in the coagulation, gastrointestinal, renal, endocrine, hepatic, respiratory, and cardiovascular systems. Additionally, we discuss how these changes can affect the processes of drug and biologic absorption, distribution, metabolism, and elimination (pharmacokinetics), and how drugs and biologics interact with biological systems, including mechanisms of drug action and effect (pharmacodynamics) during pregnancy, as well as the potential for drug‐induced toxicity and adverse effects in the mother and developing fetus. The article also examines the implications of these changes for the use of drugs and biologics during pregnancy, including consequences of suboptimal plasma drug concentrations, effect of pregnancy on the pharmacokinetics and pharmacodynamics of biologics, and the need for careful monitoring and individualized drug dosing. Overall, this article aims to provide a comprehensive understanding of the physiologic changes during pregnancy and their effects on drug and biologic metabolism to improve the safe and effective use of drugs.

The optimal dosage of aspirin for preventing preeclampsia in high‐risk pregnant women: A network meta‐analysis of 23 randomized controlled trials

“…Individual responses to aspirin may be determined by genetic, physiological, and environmental factors. For instance, variations in genes involved in drug metabolism (such as cytochrome P450 enzymes 57 ) can impact the rate of aspirin metabolism, while polymorphisms in genes related to platelet function and coagulation (such as COX‐1 and GP1BA 58 ) may affect the efficacy of aspirin in inhibiting platelet aggregation. Therefore, healthcare providers should consider these genetic and physiological factors when devising personalized aspirin dosing regimens to balance treatment effectiveness and safety.…”

Increased Risk of Gestational Hypertension by Periconceptional Exposure to Ambient Air Pollution and Effect Modification by Prenatal Depression

“…Estrogen, a vasodilating hormone, drops after ovulation, while progesterone starts to increase and continues increasing in early pregnancy. 31 Progesterone plays a critical role in signaling the maternal circulatory system during pregnancy to relax vascular smooth muscle, thus decreasing peripheral resistance and blood pressure. 31 When pregnant individuals are exposed to air pollution, their blood pressure regulation could be disrupted through upregulated sympathetic nervous system and basal systemic vascular tone, heightened oxidative stress, and chronic inflammation.…”

“…31 Progesterone plays a critical role in signaling the maternal circulatory system during pregnancy to relax vascular smooth muscle, thus decreasing peripheral resistance and blood pressure. 31 When pregnant individuals are exposed to air pollution, their blood pressure regulation could be disrupted through upregulated sympathetic nervous system and basal systemic vascular tone, heightened oxidative stress, and chronic inflammation. 11 These environmentally induced disruptions may influence the dynamic hormonal regulation from the time of the last menstrual period to the first trimester, increasing the risk of GH.…”

Physiologically Based Pharmacokinetic Modeling in Pregnancy, during Lactation and in Neonates: Achievements, Challenges and Future Directions

“…In contrast to this extensive intra- and interpatient variability, pregnant and lactating subjects and their infants are significantly underrepresented in clinical trials, leading to a dearth of in-depth information on pharmacokinetics in these populations [ 3 ]. Consequently, dosing regimens are often simply extrapolated from non-pregnant to pregnant and lactating women or allometrically scaled from adults to neonates, entailing, in both cases, considerable risks of sub-therapeutic or toxic drug effects for the mother, fetus and/or neonate [ 1 , 2 , 4 ].…”