[Bioavailability of isosorbide-5-mononitrate from delayed-action formulations]

Area of Science:

• Pharmacokinetics
• Drug bioavailability
• Cardiovascular pharmacology

Background:

• Isosorbide-5-mononitrate (IS-5-MN) is a key vasodilator.
• Optimizing IS-5-MN delivery is crucial for consistent therapeutic effects.
• Standard-release formulations require frequent dosing, potentially impacting patient adherence.

Purpose of the Study:

• To determine the relative bioavailability of IS-5-MN from sustained-release (SR) capsules compared to standard-release (SR) tablets.
• To assess drug accumulation with different IS-5-MN dosing regimens.
• To evaluate dose proportionality of peak plasma levels for SR IS-5-MN formulations.

Main Methods:

• A randomized, cross-over study involving 12 healthy subjects.
• Administration of IS-5-MN: 20 mg standard-release tablets, 20 mg SR capsules (12-h intervals), 40 mg SR capsules (24-h intervals), and 60 mg SR capsules (24-h intervals).
• Plasma concentrations of IS-5-MN were measured to calculate bioavailability and accumulation factors.

Main Results:

• Bioavailability of IS-5-MN from 20 mg, 40 mg, and 60 mg SR capsules was 79%, 67%, and 70% respectively, relative to standard-release tablets.
• Negligible drug accumulation occurred with 24-h dosing of 40 mg and 60 mg SR capsules.
• Peak plasma levels of IS-5-MN showed a linear relationship with administered doses for SR capsules.

Conclusions:

• Sustained-release IS-5-MN capsules offer favorable bioavailability and predictable pharmacokinetic profiles.
• 24-hour dosing regimens for 40 mg and 60 mg SR IS-5-MN capsules minimize drug accumulation.
• SR IS-5-MN formulations provide a viable alternative to standard-release tablets, potentially improving dosing convenience.