Pulmonary First-Pass and Steady-State Metabolism of Phenols

Purpose. To study (A) the effect of the administration route (i.v. and i.t.) on pre- and post-absorptive metabolism of phenol and 1-naphthol by the lung and (B) pulmonary extraction of phenol at steady-state.Methods. Phenols were administered intra-arterially, intravenously and intratracheally and the pre- and post-absorptive metabolism assessed by comparing the AUCs in arterial blood. Phenol was infused to steady-state and the pulmonary extraction assessed by measuring jugular vein and carotid artery blood concentrations.Results. In contrast to previously published data (e.g., Mistry and Houston, Drug Metab. Dispos. 13:740–745 (1985)) we could not detect pulmonary first-pass metabolism of the phenols; reasons for this disparity are discussed. An apparent negative pulmonary extraction of phenol at steady-state was observed, probably as a consequence of extraction by organs which are in series, and not parallel, with the lungs (e.g. liver, kidneys and GIT).Conclusions. (A) Phenol and 1-naphthol do not undergo pulmonary first-pass metabolism. (B) Traditional methods of assessing organ extraction and clearance at steady-state cannot be utilised when metabolising organs are in series.