PMID- 19398502
OWN - NLM
STAT- MEDLINE
DCOM- 20090928
LR  - 20181201
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 37
IP  - 7
DP  - 2009 Jul
TI  - Characterization of the binding of drugs to human intestinal fatty acid binding 
      protein (IFABP): potential role of IFABP as an alternative to albumin for in 
      vitro-in vivo extrapolation of drug kinetic parameters.
PG  - 1395-403
LID - 10.1124/dmd.109.027656 [doi]
AB  - This work characterized for the first time the binding of acidic, neutral, and 
      basic drugs to human intestinal fatty acid binding protein (IFABP) and, for 
      comparison, to bovine serum albumin (BSA). In addition, the study investigated 
      whether IFABP can substitute for BSA as a constituent in incubations of human 
      liver microsomes (HLMs) in in vitro-in vivo extrapolation (IV-IVE) studies. Each 
      molecule of purified IFABP bound a single molecule of the fluorescent probe 
      1-anilino-8-naphthalene sulfonate or arachidonic acid with K(d) values similar to 
      those reported for rat IFABP. Basic drugs bound negligibly to IFABP. Based on 
      fraction unbound (f(u)) at a protein concentration of 0.5% (w/v), binding of 
      acidic and neutral drugs ranged from minor (f(u) > 0.8) to moderate (f(u) 
      0.5-0.8). Of the compounds screened, highest binding to IFABP was observed for 
      sulfinpyrazone (an acid) and beta-estradiol (a neutral compound). However, 
      binding to IFABP was lower than to BSA for all the drugs investigated. To 
      determine the potential suitability of IFABP as an alternative to BSA for 
      enhancing the prediction accuracy of IV-IVE based on human liver microsomal 
      kinetic data, the kinetics of zidovudine (AZT) glucuronidation by HLM were 
      characterized in the absence and presence of BSA and IFABP (0.5-2.5%, w/v). Each 
      protein reduced the K(m) for AZT glucuronidation in a concentration-dependent 
      manner, although a higher content of IFABP in incubations (2.5 versus 1-1.5% for 
      BSA) was necessary for a 10-fold reduction in this parameter. The results 
      indicate that IFABP is likely to have advantages over BSA in microsomal kinetic 
      studies with drugs that bind extensively to albumin.
FAU - Rowland, Andrew
AU  - Rowland A
AD  - Department of Clinical Pharmacology, Flinders University School of Medicine, 
      Flinders Medical Centre, Bedford Park, SA 5042, Australia.
FAU - Knights, Kathleen M
AU  - Knights KM
FAU - Mackenzie, Peter I
AU  - Mackenzie PI
FAU - Miners, John O
AU  - Miners JO
LA  - eng
PT  - Journal Article
DEP - 20090427
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Albumins)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Glucuronides)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Sulfonamides)
RN  - 0 (oxysterol binding protein)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 4B9XT59T7S (Zidovudine)
RN  - 6158TKW0C5 (Phenytoin)
RN  - W31X2H97FB (Torsemide)
SB  - IM
MH  - Albumins
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Binding, Competitive
MH  - Cattle
MH  - Cell Line
MH  - Circular Dichroism
MH  - Fatty Acid-Binding Proteins/*metabolism
MH  - Glucuronides/*metabolism
MH  - Humans
MH  - Mutagenesis, Site-Directed
MH  - Phenytoin/metabolism
MH  - Receptors, Steroid/*metabolism
MH  - Serum Albumin, Bovine/*metabolism
MH  - Sulfonamides/metabolism
MH  - Thermodynamics
MH  - Torsemide
MH  - Zidovudine/metabolism
EDAT- 2009/04/29 09:00
MHDA- 2009/09/29 06:00
CRDT- 2009/04/29 09:00
PHST- 2009/04/29 09:00 [entrez]
PHST- 2009/04/29 09:00 [pubmed]
PHST- 2009/09/29 06:00 [medline]
AID - dmd.109.027656 [pii]
AID - 10.1124/dmd.109.027656 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2009 Jul;37(7):1395-403. doi: 10.1124/dmd.109.027656. Epub 
      2009 Apr 27.