Abstract
The aim of this study was to synthesize an ester with low lipophilicity, and to use this ester to further investigate pre-absorptive pulmonary first-pass metabolism. Hexanoic acid phenethyl ester was synthesized by reacting 2-phenylethanol with hexanoyl chloride. Pre-absorptive first-pass metabolism was assessed by comparing the areas under the blood concentration-time curves after intra-arterial administration of the hexanoic acid phenethyl ester with those after intratracheal instillation. Hexanoic acid phenethyl ester experienced extensive first-pass metabolism (53% of the absorbed dose) before or during absorption. This and earlier data suggests that the extent of this first-pass extraction is dependent on the physicochemical properties of the ester and in particular whether a compound experiences diffusion-limited absorption. Pre-absorptive pulmonary first-pass metabolism of compounds whose absorption iS diffusion-rate limited may be extensive even when pulmonary enzyme expression is low. This has consequences for the systemic delivery of drugs and in particular esters via the lungs.
Original language | English |
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Pages (from-to) | 441-445 |
Number of pages | 5 |
Journal | Pharmacy and Pharmacology Communications |
Volume | 6 |
Issue number | 10 |
Publication status | Published - 1 Jan 2000 |