Route dependent pulmonary first-pass metabolism of a series of biphenylacetic acid esters in rats.
The influence of route of administration of a series of biphenylacetic acid aliphatic esters on their pulmonary first-pass metabolism in rats was investigated. The results were compared with in vitro data and with the physicochemical properties of the esters. Pre- and post-absorptive first-pass metabolism was assessed by comparing area under blood concentration-time curves after intra-arterial administration of the esters with those seen after intravenous (to assess post-absorptive) and intratracheal (to assess pre-absorptive) administration. The extent of pulmonary metabolism was dependent on the route of administration. For all the esters studied there was insignificant post-absorptive first-pass extraction, however there was a large pre-absorptive first-pass extraction (greater than 80%). Enzyme kinetics derived in vitro using the 'well-stirred' model (Dickinson and Taylor, 1995. Int. J. Pharm. 116, 231-236) predicted the extent of post-absorptive but not the pre-absorptive, first-pass metabolism.
Dickinson
P A
PA
Welsh School of Pharmacy, UWC, Cathays Park, Cardiff CF1 3XF, UK. dickinsonpa@cardiff.ac.uk
Taylor
G
G
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004655:Emulsions; D004952:Esters; D006207:Half-Life; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010648:Phenylacetates / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions; D013535:Suspensions
D004655:Emulsions; D004952:Esters; D010648:Phenylacetates; D012996:Solutions; D013535:Suspensions; C510486:dodecyl biphenylacetate; C510487:hexyl biphenylacetate; C510488:octyl biphenylacetate; C048480:4-biphenylylacetic acid ethyl ester