Pharmacokinetics and bioavailability of intravenous and topical nitroglycerin in the rhesus monkey: estimate of percutaneous first-pass metabolism.

[14C]Nitroglycerin was administered intravenously and topically to three rhesus monkeys and the pharmacokinetics were determined. The rhesus monkey is an animal model for which percutaneous absorption is similar to that in the human. After intravenous administration the decline in plasma nitroglycerin concentration was biexponential with an initial half-life of 0.8 min (2-5 min postadministration) and a terminal half-life of 18 min (5-60 min postadministration). After topical application in an ointment, plasma concentrations of unchanged nitroglycerin were first detectable at 0.25 hr postapplication. Peak plasma nitroglycerin concentrations occurred between 4-6 hr, and nitroglycerin was still detectable at 24 hr postapplication. Plasma levels fit a biexponential curve with an alpha-phase half-life of 3.0 hr, a beta-phase half-life of 4.3 hr, and a lag time of 0.5 hr. The absolute bioavailability of topical nitroglycerin was 56.6 +/- 5.8%. The differences in bioavailability estimates between unchanged nitroglycerin and total carbon-14 is considered to be the amount of nitroglycerin which is metabolized as it is absorbed through the skin (percutaneous first-pass effect). This value for topical nitroglycerin was quite small, only 16-21% depending on the method of comparison.