Effect of sesame oil emulsion on nitroglycerin pharmacokinetics

When nitroglycerin (3.5 mg/kg) was administered orally in a 20% sesame oil emulsion to rats, peak plasma concentrations were decreased but bioavauability was unaffected when compared to those observed using an aqueous solution vehicle. Pre-dosing with drug-free emulsion for 3 days, however, caused significant increases in nitroglycerin biovailability (2.5X) and peak plasma concentrations (5X) compared to controls. This increase appeared to be reversible when emulsion dosing was withdrawn. The apparent increase in bioavailability was not due to a change in nitroglycerin distribution or elimination kinetics from drug-free emulsion administration nor could it be attributed to the surfactant used. There was no change in in vitro liver organic nitrate reductase activity or reduced glutathione concentration with emulsion pretreatment. The results suggested that, when using emulsion as a dosage form, repeated dosing of the vehicle could have an effect on the drug absorption process that was not predicted from single dose administration.