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Drug Metabolism and Disposition Fast Forward
First published on July 24, 2008; DOI: 10.1124/dmd.108.020842

0090-9556/08/3610-2086-2092$20.00
DMD 36:2086-2092, 2008

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Effect of Albumin on the Biliary Clearance of Compounds in Sandwich-Cultured Rat Hepatocytes

Kristina K. Wolf, Kenneth R. Brouwer, Gary M. Pollack, and Kim L. R. Brouwer

Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (K.K.W., G.M.P., K.L.R.B.); and Qualyst, Inc., Raleigh, North Carolina (K.R.B.)

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 Formula) 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 Formula of these compounds. Surprisingly, BSA-FAF decreased both BEI and intrinsic Formula for digoxin and pravastatin, which represent low and moderately bound compounds, respectively. The BEI and intrinsic Formula 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 Formula 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.

Address correspondence to: Kim L. R. Brouwer, 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. E-mail: kbrouwer{at}unc.edu






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