Drug disposition in mother and foetus

Area of Science:

• Pharmacology
• Obstetrics
• Developmental Biology

Background:

• Pregnancy significantly alters maternal physiology, affecting drug pharmacokinetics.
• Reduced serum albumin in pregnancy impacts drug protein binding.
• Increased maternal cardiac output enhances renal function and drug clearance.

Purpose of the Study:

• To elucidate the pharmacokinetic changes during pregnancy.
• To understand drug transfer across the placenta.
• To evaluate fetal drug metabolism and elimination pathways.

Main Methods:

• Review of physiological changes during pregnancy affecting drug disposition.
• Analysis of placental transfer mechanisms for lipophilic and hydrophilic compounds.
• Examination of fetal hepatic and renal drug processing capabilities.

Main Results:

• Increased maternal renal plasma flow, glomerular filtration rate, and creatinine clearance lead to higher renal drug clearance.
• Efficient placental transfer of lipophilic drugs; slower transfer of hydrophilic drugs.
• Limited fetal drug metabolism due to immature hepatic enzymes and unique liver circulation (ductus venosus shunt).
• Ineffective fetal renal elimination due to low renal blood flow and lack of tubular secretion, with drug recirculation via amniotic fluid.

Conclusions:

• Maternal pharmacokinetic alterations and placental permeability significantly influence fetal drug exposure.
• Immature fetal elimination pathways contribute to prolonged drug exposure in the fetus.
• Understanding these factors is crucial for safe medication use during pregnancy.