The effect of protein binding on the hepatic first pass of O-acyl salicylate derivatives in the rat
Data(s) |
01/01/1998
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Resumo |
In this work the in-situ perfused rat liver has been used to examine the effect of changing the protein content of the perfusate on the hepatic extraction of O-acyl esters of salicylic acid. The hepatic availability (F) of these solutes was studied at a flow-rate of 30 mt min(-1) with perfusate albumin concentrations of 0, 2, and 4% w/v. The hepatic availability of the esters was shown to decrease with increasing carbon-chain length in the O-acyl group; for all the esters the hepatic availability increased with increasing albumin concentration in the perfusate. The dispersion-model-derived efficiency number (R-N) Of the esters was shown to increase with increasing lipophilicity and decrease with increasing albumin concentration in the perfusate. The unbound fraction (f(u),) of the esters decreased with lipophilicity. R-N/f(u), for acetylsalicylic acid remained relatively constant as the albumin concentration was increased. However, R-N/f(u), for n-pentanoyl- and n-hexanoylsalicylic acids increased significantly as albumin concentration increased from 0% to 4%. Thus, for the more lipophilic solutes (n-pentanoyl- and n-hexanoylsalicylic acids) the presence of albumin apparently facilitates the uptake of unbound solute relative to acetylsalicylic acid. |
Identificador | |
Idioma(s) |
eng |
Publicador |
Pharmaceutical Press |
Palavras-Chave | #Pharmacology & Pharmacy #Albumin Receptor #Rose-bengal #Mediated Transport #Cell-surface #Liver #Dissociation #Acid #Taurocholate #Facilitation #Substances #1115 Pharmacology and Pharmaceutical Sciences |
Tipo |
Journal Article |