Bioavailability of disopyramide in normal volunteers using unbound concentration

Area of Science:

• Pharmacology
• Clinical Pharmacy
• Drug Metabolism

Background:

• Disopyramide is an antiarrhythmic drug with variable bioavailability.
• Understanding its pharmacokinetic profile is crucial for effective dosing.
• Plasma protein binding can influence drug disposition.

Purpose of the Study:

• To determine the pharmacokinetics of disopyramide in healthy volunteers.
• To assess the impact of saturable protein binding on disopyramide bioavailability.
• To compare unbound and total drug concentrations in pharmacokinetic analysis.

Main Methods:

• Administered oral (300 mg) and intravenous (2 mg/kg) disopyramide doses to 10 healthy volunteers.
• Measured plasma concentrations over time to determine pharmacokinetic parameters.
• Calculated unbound and total clearance, elimination rate constants, and bioavailability.
• Assessed plasma protein binding to identify potential saturation.

Main Results:

• Unbound clearance was 599 ml/min and unbound renal clearance was 310 ml/min.
• Terminal elimination half-life of unbound disopyramide was approximately 3.85 hours.
• Oral absorption rate constant was 0.53 h⁻¹, with peak concentrations at 3.2 hours.
• Bioavailability calculated from unbound concentrations was 0.809.
• Bioavailability calculated from total concentrations was 0.813, similar to unbound values despite saturable binding.

Conclusions:

• Disopyramide exhibits predictable pharmacokinetics with high bioavailability in healthy individuals.
• Saturable plasma protein binding did not significantly alter overall bioavailability calculations.
• These findings support consistent dosing strategies for disopyramide therapy.