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The fate of salicylate in the plasma of rats was followed after nasal, intravenous, and oral administration of 2.0-mg doses of aspirin. Aspirin was well absorbed following nasal administration of a neutralized, nonirritating solution containing triethanolamine. The rate of absorption was slower than that of other nasally administered drugs, such as propranolol or progesterone. The bioavailability of aspirin following nasal administration was 100%, whereas the oral bioavailability was only 58.8% at the dose studied.

To study the factors influencing nasal absorption of a model pentapeptide, plasma levels of total radioactivity were determined following the administration of [3H]tyr-leucine enkephalin to rats intravenously, intranasally alone, and intranasally in the presence of puromycin. The major pathway for transport of radioactivity into the blood from the nasal cavity appeared to be hydrolysis of [3H]tyr-leucine enkephalin to [3H]L-tyrosine, followed by absorption of [3H]L-tyrosine. When puromycin was added to the nasal solution in concentrations at which the in vitro hydrolysis of leucine enkephalin was completely inhibited, the appearance of radioactivity in the plasma was slowed, but plasma concentrations of radioactivity eventually reached levels comparable to those observed in the absence of puromycin. In view of the inhibitory effect of puromycin on the hydrolysis of leucine enkephalin, it was assumed that a significant fraction of the [3H]tyr-leucine enkephalin was absorbed intact in the presence of this substance. However, an assay method for intact leucine enkephalin in plasma is needed to confirm these preliminary observations.

The nasal absorption of a model peptide, leucine enkephalin (LE), was studied in rats using an in situ technique in which 4 mL of perfusion solution was circulated. Leucine enkephalin (LE) was found to undergo hydrolysis to its major metabolite des-tyrosine leucine enkephalin (DTLE). The addition of 1% sodium glycocholate (SGC) to the perfusion solution resulted in an increase in the overall rate of disappearance of LE and a decrease in the rate of formation of DTLE. When LE was added to nasal washings (i.e., Ringer's buffer that was precirculated through the nasal cavity to extract enzymes), LE was found to form DTLE. When SGC or puromycin was added to the nasal washings prior to the addition of LE, the rate of conversion of LE to DTLE was significantly reduced, suggesting that these two agents can inhibit peptidase enzyme activity in the nasal cavity. Since the volume of the solution has been shown to influence the kinetics of absorption of drugs administered nasally, a new experimental technique, the in vivo-in situ technique, which utilizes small volumes of solution and simulates realistic use of nose drops, was employed to further examine the mechanism of absorption and hydrolysis of LE in rats. Leucine enkephalin (LE) dissolved in 100 microL of Ringer's buffer was placed in the isolated nasal cavities of rats. The disappearance of LE and the appearance of DTLE were followed by rinsing the nasal cavity with fresh buffer. Disappearance of LE was always accompanied by appearance of DTLE, and the fraction of LE converted to DTLE decreased as the concentration of LE increased, suggesting a saturable enzymatic process.(ABSTRACT TRUNCATED AT 250 WORDS)