Table 2.

Pathophysiological changes in pregnant women that can impact pharmacokinetics of certain drugs.

Changes	Potential impact on pharmacokinetics
Physiologic changes
Nausea and vomiting	↓ Absorption (↓ peak conc. and ↓ oral bioavailability)
Delayed motility	Delayed absorption (↑ time to peak conc.)
Decreased gastric acid secretion	↓ Oral bioavailability for anionic drugs
Body weight gain	↑ Apparent volume of distribution
Body fat gain	↑ Apparent volume of distribution for lipophilic drugs
Increased plasma volume	↑ Apparent volume of distribution
Decreased plasma albumin and αl-acid glycoprotein	↑ Unbound drug concentration for high clearance drugs; unbound drug concentration not expected to be altered for low clearance drugs. (It is important to base therapy on unbound drug, for drugs that are highly bound.)
Changes in hepatic drug-metabolizing enzymes	Altered hepatic clearance for low extraction ratio drugs administered intravenously or high extraction drugs administered orally
Increased hepatic blood flow	↑Hepatic clearance for high extraction ratio drugs
Increased renal blood flow	↑ Renal clearance for unchanged drug
Increased glomerular filtration	↑ Renal clearance for unchanged drug
Other maternal factors
Chronic disease or pregnancy complications	Changes in ADMET/PD
Maternal poly-pharmacy	PK/PD drug interactions
Maternal–Fetal factors
Placenta	Placental drug metabolism, placental transporters
Fetus	Hepatic CYP3A7 does not contribute to clearance in mother, but it can influence concentration of drug and metabolites in the fetus and ↑ apparent volume of distribution
Amniotic fluid	Drug accumulation and ↑ apparent volume of distribution

Note: ↑, increase; ↓, decrease; CYP, cytochrome P450; PK, pharmacokinetics; PD, pharmacodynamics; ADME drug, absorption, distribution, metabolism, and excretion.