Nitroglycerin concentration in plasma: comparison between transdermal therapeutic system and ointment

Area of Science:

• Pharmacology
• Dermatology
• Cardiovascular Medicine

Background:

• Nitroglycerin is a vasodilator used to treat angina.
• Transdermal drug delivery systems offer advantages in controlling drug release and improving patient compliance.
• Comparing different topical nitroglycerin formulations is crucial for optimizing therapeutic outcomes.

Purpose of the Study:

• To evaluate the plasma concentration time course of nitroglycerin from a transdermal system (TTS-nitroglycerin).
• To compare the bioavailability of nitroglycerin from TTS-nitroglycerin versus traditional nitroglycerin ointment.
• To assess pharmacokinetic parameters and side effects associated with each delivery method.

Main Methods:

• A double-blind, cross-over study involving 12 healthy male volunteers.
• Administration of TTS-nitroglycerin and sequential applications of 2% nitroglycerin ointment.
• Measurement of plasma nitroglycerin concentrations over time.
• Analysis of pharmacokinetic parameters including area under the curve (AUC) and clearance.

Main Results:

• Mean available nitroglycerin amounts were 15.8 mg for TTS-nitroglycerin and 9.8 mg for ointment.
• Plasma concentrations ranged from 10-18 pg/ml-cm2 for both treatments.
• Normalized AUCs (353 vs. 410 pg/hr/ml-cm2) and clearance ratios (0.98) did not differ significantly between the two forms.
• Subjects experienced mild-to-moderate nitrate therapy side effects, including hypotension and tachycardia, with both formulations.

Conclusions:

• TTS-nitroglycerin and nitroglycerin ointment provide comparable nitroglycerin bioavailability.
• Both transdermal systems and ointment applications lead to similar pharmacokinetic profiles.
• Clinical monitoring for side effects like decreased blood pressure and increased heart rate is warranted for both topical nitroglycerin formulations.