Elevated plasma glycoproteins in fetal sheep do not bind basic lipophilic drugs

Area of Science:

• Pharmacology
• Biochemistry
• Developmental Biology

Background:

• N-acetylneuraminic acid (NANA)-containing glycoproteins are key in adult plasma drug binding.
• Alpha 1-acid glycoprotein (AGP) is the primary binding protein for basic lipophilic drugs in adults.

Purpose of the Study:

• To evaluate the role of NANA-containing glycoproteins in fetal sheep plasma drug binding.
• To compare drug binding in fetal versus maternal sheep plasma.

Main Methods:

• Measurement of NANA concentrations in fetal and maternal sheep plasma.
• Assessment of propranolol, lidocaine, and methadone binding to plasma proteins.
• Calculation of bound-to-free drug concentration ratios.

Main Results:

• Fetal sheep plasma had significantly higher NANA concentrations than maternal plasma.
• Despite higher NANA, fetal drug binding was only 20-36% of maternal levels.
• NANA concentration did not correlate with drug binding in fetal plasma.

Conclusions:

• NANA-containing glycoproteins do not reliably predict basic lipophilic drug binding in fetal sheep plasma.
• AGP levels or function may differ significantly between fetal and adult sheep.
• Further research is needed to understand drug disposition in fetal mammals.