PMID- 22331994
OWN - NLM
STAT- MEDLINE
DCOM- 20120823
LR  - 20171116
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
VI  - 40
IP  - 5
DP  - 2012 May
TI  - Effect of albumin on human liver microsomal and recombinant CYP1A2 activities: 
      impact on in vitro-in vivo extrapolation of drug clearance.
PG  - 982-9
LID - 10.1124/dmd.111.044057 [doi]
AB  - Long-chain unsaturated fatty acids inhibit several cytochrome P450 and 
      UDP-glucuronosyltransferase (UGT) enzymes involved in drug metabolism, including 
      CYP2C8, CYP2C9, UGT1A9, UGT2B4, and UGT2B7. Bovine serum albumin (BSA) enhances 
      these cytochrome P450 and UGT activities by sequestering fatty acids that are 
      released from membranes, especially with human liver microsomes (HLM) as the 
      enzyme source. Here, we report the effects of BSA on CYP1A2-catalyzed phenacetin 
      (PHEN) O-deethylation and lidocaine (LID) N-deethylation using HLM and 
      Escherichia coli-expressed recombinant human CYP1A2 (rCYP1A2) as the enzyme 
      sources. BSA (2% w/v) reduced (p < 0.05) the K(m) values of the high-affinity 
      components of human liver microsomal PHEN and LID deethylation by approximately 
      70%, without affecting V(max). The K(m) (or S(50)) values for PHEN and LID 
      deethylation by rCYP1A2 were reduced to a similar extent. A fatty acid mixture, 
      comprising 3 muM concentrations each of oleic acid and linoleic acid plus 1.5 muM 
      arachidonic acid, doubled the K(m) value for PHEN O-deethylation by rCYP1A2. 
      Inhibition was reversed by the addition of BSA. K(i) values for the individual 
      fatty acids ranged from 4.7 to 16.7 muM. Single-point in vitro-in vivo 
      extrapolation (IV-IVE) based on the human liver microsomal kinetic parameters 
      obtained in the presence, but not absence, of BSA predicted in vivo hepatic 
      clearances of PHEN O-deethylation and LID N-deethylation that were comparable to 
      values reported in humans, although in vivo intrinsic clearances were 
      underpredicted. Prediction of the in vivo clearances of the CYP1A2 substrates 
      observed here represents an improvement on other experimental systems used for 
      IV-IVE.
FAU - Wattanachai, Nitsupa
AU  - Wattanachai N
AD  - Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 
      Thailand.
FAU - Tassaneeyakul, Wichittra
AU  - Tassaneeyakul W
FAU - Rowland, Andrew
AU  - Rowland A
FAU - Elliot, David J
AU  - Elliot DJ
FAU - Bowalgaha, Kushari
AU  - Bowalgaha K
FAU - Knights, Kathleen M
AU  - Knights KM
FAU - Miners, John O
AU  - Miners JO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120213
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Cytochrome P-450 CYP1A2 Inhibitors)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 98PI200987 (Lidocaine)
RN  - EC 1.14.14.1 (CYP1A2 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
RN  - ER0CTH01H9 (Phenacetin)
SB  - IM
MH  - Animals
MH  - Catalysis
MH  - Cattle
MH  - Chromatography, High Pressure Liquid
MH  - Cytochrome P-450 CYP1A2/genetics/*metabolism
MH  - Cytochrome P-450 CYP1A2 Inhibitors
MH  - Escherichia coli/enzymology/genetics
MH  - Fatty Acids, Unsaturated/chemistry/metabolism/pharmacology
MH  - Humans
MH  - Kinetics
MH  - Lidocaine/*metabolism
MH  - Mass Spectrometry
MH  - Metabolic Clearance Rate
MH  - Microsomes, Liver/drug effects/*enzymology
MH  - Models, Biological
MH  - Phenacetin/*metabolism
MH  - Predictive Value of Tests
MH  - Serum Albumin, Bovine/*pharmacology
MH  - Substrate Specificity
EDAT- 2012/02/15 06:00
MHDA- 2012/08/24 06:00
CRDT- 2012/02/15 06:00
PHST- 2012/02/15 06:00 [entrez]
PHST- 2012/02/15 06:00 [pubmed]
PHST- 2012/08/24 06:00 [medline]
AID - dmd.111.044057 [pii]
AID - 10.1124/dmd.111.044057 [doi]
PST - ppublish
SO  - Drug Metab Dispos. 2012 May;40(5):982-9. doi: 10.1124/dmd.111.044057. Epub 2012 
      Feb 13.