Pulmonary first-pass and steady-state metabolism of phenols.
OBJECTIVE
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.l3:740-745 (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.
Dickinson
P A
PA
Welsh School of Pharmacy, University of Wales, Cardiff, U.K.
Taylor
G
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008168:Lung / Q000378:metabolism*; D008297:Male; D009284:Naphthols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019800:Phenol; D010636:Phenols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D014132:Trachea
D009284:Naphthols; D010636:Phenols; C029350:1-naphthol; D019800:Phenol