Pharmacokinetics of Antianginal Drugs

Pharmacokinetics of Antianginal Drugs

The pharmacokinetics of antianginal drugs vary significantly among different classes and individual agents. Understanding these properties is crucial for optimal drug selection, dosing, and management of potential drug interactions. Here's an overview of the pharmacokinetics for major classes of antianginal drugs:

Nitrates:

a) Absorption: Nitroglycerin is rapidly absorbed through the oral mucosa, with sublingual tablets providing effects within 1-3 minutes. Transdermal patches and ointments offer slower, sustained absorption.

b) Distribution: Nitrates are widely distributed throughout the body, with minimal protein binding.

c) Metabolism: Primarily hepatic, involving glutathione-organic nitrate reductase.

d) Elimination: Mainly renal excretion of metabolites, with short half-lives (1-4 hours for most nitrates).

e) Bioavailability: Sublingual nitroglycerin has nearly 100% bioavailability, while oral isosorbide dinitrate has lower bioavailability due to first-pass metabolism.

Beta-blockers:

a) Absorption: Generally well-absorbed orally, with peak plasma concentrations reached within 1-4 hours.

b) Distribution: Varies among agents; lipophilic beta-blockers (e.g., metoprolol) cross the blood-brain barrier more readily than hydrophilic ones (e.g., atenolol).

c) Metabolism: Mostly hepatic, with some agents (e.g., atenolol) excreted unchanged in urine.

d) Elimination: Half-lives range from 3-4 hours (e.g., esmolol) to 14-24 hours (e.g., bisoprolol).

e) Bioavailability: Varies widely, from about 30% for propranolol to nearly 100% for certain agents like timolol.

Calcium Channel Blockers:

a) Absorption: Well-absorbed orally, with peak plasma concentrations typically reached within 1-6 hours.

b) Distribution: Highly protein-bound (90-99%) for most agents.

c) Metabolism: Extensively metabolized in the liver, primarily by CYP3A4 enzymes.

d) Elimination: Half-lives vary from 2-5 hours for short-acting agents to 30-50 hours for long-acting formulations.

e) Bioavailability: Generally low due to significant first-pass metabolism, ranging from 10-40% for most agents.

Ranolazine:

a) Absorption: Well-absorbed orally, with peak plasma concentrations reached in 2-6 hours.

b) Distribution: Approximately 62% protein-bound.

c) Metabolism: Primarily hepatic, via CYP3A4 and CYP2D6 enzymes.

d) Elimination: Half-life of 7-9 hours.

e) Bioavailability: Approximately 70%, with food increasing absorption rate but not extent.

Ivabradine:

a) Absorption: Rapidly and almost completely absorbed after oral administration.

b) Distribution: Approximately 70% protein-bound.

c) Metabolism: Extensively metabolized in the liver and intestine by CYP3A4.

d) Elimination: Half-life of 11 hours for the parent compound.

e) Bioavailability: About 40% due to first-pass effect.

Trimetazidine:

a) Absorption: Rapidly absorbed orally, with peak plasma concentrations reached within 2 hours.

b) Distribution: Limited protein binding (approximately 16%).

c) Metabolism: Primarily hepatic, with no significant involvement of cytochrome P450 enzymes.

d) Elimination: Mainly renal, with a half-life of about 7 hours.

e) Bioavailability: Approximately 90%.

Nicorandil:

a) Absorption: Rapidly absorbed after oral administration, with peak plasma levels within 30-60 minutes.

b) Distribution: Minimal protein binding (approximately 25%).

c) Metabolism: Hepatic metabolism, with the formation of several metabolites.

d) Elimination: Half-life of about 1 hour.

e) Bioavailability: Nearly 75-80%.

Understanding these pharmacokinetic properties is essential for optimizing antianginal therapy.