Abstract
The airway-to-blood absorption of the μ-selective opioid tetrapeptide agonist Tyr-D-Arg-Phe-Phe-NH2 (MW 631) was investigated in the isolated, perfused, and ventilated rat lung model. The lung metabolism of the peptide was compared after airway and vascular delivery. The concentrations of the parent tetrapeptide and five of its metabolites in the perfusate and in bronchoalveolar lavage fluid were analyzed by LC-MS.The metabolism of the peptide was higher after delivery to the airways compared to vascular delivery. However, the tetrapeptide was highly transported from the air-to-blood side to an extent of 47.8 ± 10.7% in 2 h. In conclusion, the results prompt investigations of the pulmonary route as a successful alternative to parenteral delivery for this tetrapeptide.
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