Effect of dose and ointment application technique on nitroglycerin plasma concentrations

Area of Science:

• Pharmacokinetics
• Dermatology
• Cardiovascular Pharmacology

Background:

• Nitroglycerin ointment (NTG-O) is used for cardiovascular conditions.
• Understanding NTG-O absorption is crucial for effective dosing.

Purpose of the Study:

• To evaluate the pharmacokinetics of nitroglycerin ointment.
• To determine the impact of dose and surface area on NTG-O absorption and plasma concentrations.

Main Methods:

• Ten healthy male volunteers received four randomized NTG-O treatments with varying doses and surface areas.
• Blood samples were collected over six hours to measure nitroglycerin plasma concentrations using gas-liquid chromatography.
• Pharmacokinetic parameters including AUC, Cmax, and Tmax were analyzed.

Main Results:

• Increasing the NTG-O dose generally doubled the area under the concentration-time curve (AUC) and peak plasma concentration (Cmax).
• Surface area did not significantly affect AUC, Cmax, or Tmax.
• Nitroglycerin plasma concentrations generally remained within the proposed therapeutic range (1.2-11.1 ng/mL) throughout the 6-hour interval.

Conclusions:

• Continuous absorption of NTG-O occurs over the 6-hour dosing interval.
• Dose is a significant factor in NTG-O absorption, with a dose-dependent increase in AUC and Cmax.
• The findings support the general principle that doubling the NTG-O dose approximately doubles the systemic absorption.