Effect of albumin on the biliary clearance of compounds in sandwich-cultured rat hepatocytes.
The purpose of the present study was to evaluate the effects of bovine serum albumin (BSA) and essentially fatty acid-free BSA (BSA-FAF) on the biliary clearance of compounds in sandwich-cultured rat hepatocytes. Unbound fraction, biliary excretion index (BEI), and unbound intrinsic biliary clearance (intrinsic Clbiliary') were determined for digoxin, pravastatin, and taurocholate in the absence or presence of BSA or BSA-FAF. BSA had little effect on the BEI or intrinsic Clbiliary' of these compounds. Surprisingly, BSA-FAF decreased both BEI and intrinsic Clbiliary' for digoxin and pravastatin, which represent low and moderately bound compounds, respectively. The BEI and intrinsic Clbiliary' of taurocholate, a highly bound compound, were not altered significantly by BSA-FAF. Neither BSA nor BSA-FAF had a discernable effect on the bile canalicular networks based on carboxydichlorofluorescein retention. Neither the addition of physiological concentrations of calcium nor the addition of fatty acids to BSA-FAF was able to restore the BEI or intrinsic Clbiliary' of the model compounds to similar values in the absence or presence of BSA. Careful consideration is warranted when selecting the type of BSA for addition to in vitro systems such as sandwich-cultured rat hepatocytes.
Wolf
Kristina K
KK
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB #7360, Kerr Hall Room 3205, Chapel Hill, NC 27599, USA.
Brouwer
Kenneth R
KR
Pollack
Gary M
GM
Brouwer
Kim L R
KL
D000818:Animals; D001659:Biliary Tract / Q000378:metabolism*; D002853:Chromatography, Liquid; D004077:Digoxin / Q000493:pharmacokinetics; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D017035:Pravastatin / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry; D013656:Taurocholic Acid / Q000493:pharmacokinetics
D012710:Serum Albumin, Bovine; D013656:Taurocholic Acid; D004077:Digoxin; D017035:Pravastatin