Chronic propranolol administration during pregnancy. Maternal pharmacokinetics

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Metabolism

Background:

• Propranolol is a widely used beta-blocker.
• Understanding its pharmacokinetics during pregnancy is crucial for maternal and fetal safety.
• Previous studies have not fully elucidated the impact of pregnancy on propranolol and its metabolites.

Purpose of the Study:

• To determine the pharmacokinetics of propranolol and its major metabolites during different trimesters of pregnancy.
• To compare these pharmacokinetic parameters with those in the postpartum period.
• To investigate potential correlations between propranolol dosage, plasma concentrations, and blood pressure response.

Main Methods:

• Pharmacokinetic analysis of propranolol, propranolol glucuronide, 4-hydroxypropranolol, 4-hydroxypropranolol glucuronide, and naphthoxylactic acid.
• Study conducted in thirteen pregnant patients across three trimesters and postpartum.
• Blood pressure and drug concentration measurements were recorded.

Main Results:

• Pharmacokinetics of propranolol and its glucuronidated and hydroxylated metabolites were not significantly altered by pregnancy.
• A positive nonlinear relationship was observed between daily propranolol dose and peak plasma concentrations.
• Naphthoxylactic acid exhibited significantly shorter elimination half-lives and smaller area under the curve values in the third trimester compared to postpartum.

Conclusions:

• Pregnancy does not significantly impact the pharmacokinetics of propranolol, propranolol glucuronide, 4-hydroxypropranolol, or 4-hydroxypropranolol glucuronide.
• The pharmacokinetics of naphthoxylactic acid are altered during pregnancy, particularly in the third trimester.
• This alteration in naphthoxylactic acid kinetics may be due to competitive inhibition of its formation by endogenous substances, possibly steroids.