Felodipine kinetics in healthy men

Area of Science:

• Pharmacology
• Clinical Pharmacology
• Drug Metabolism

Background:

• Felodipine is a calcium channel blocker used to treat hypertension.
• Understanding its pharmacokinetic profile is crucial for optimizing therapeutic use.

Purpose of the Study:

• To characterize the absorption, distribution, and elimination of intravenous and oral felodipine.
• To determine the bioavailability and pharmacokinetic parameters of felodipine in healthy male subjects.

Main Methods:

• Randomized, crossover study design.
• Administration of 2.5 mg intravenous (IV) infusion and 27.5 mg oral solution of 14C-felodipine.
• Analysis of plasma concentrations and urinary/fecal excretion of radioactivity.

Main Results:

• Oral felodipine showed rapid absorption (peak concentration at 64 min) but low bioavailability (16%) due to significant presystemic elimination.
• Pharmacokinetics followed a multicompartmental model with distinct distribution and elimination phases.
• Terminal elimination half-life (t1/2) was approximately 10.2 hours.
• Total body clearance was 1.2 L/min.
• 62-81% of the dose was excreted as metabolites in urine and feces within 72 hours.

Conclusions:

• Oral felodipine is rapidly absorbed but undergoes substantial first-pass metabolism, leading to reduced bioavailability.
• The drug distributes widely in the body and is eliminated through metabolism, with excretion in urine and feces.
• These findings are important for understanding felodipine's pharmacokinetics and guiding clinical dosing.