title: Influences of artificial heart-lung machine operation on the binding sites of albumin: possibility of an effective administration plan.
abstract: OBJECTIVE
  The purpose of this study is to investigate the influence of changes in the human serum albumin (HSA) and free fatty acid (FFA) on alteration of the binding abilities of sites I and II after the operation of an artificial heart-lung machine.
  
  
  METHODS
  The binding abilities of phenytoin (site I) and diazepam (site II) to patients' sera collected before and after the operation of an artificial heart-lung machine and pseudopatient serum samples were examined by ultra-filtration.
  
  
  RESULTS
  The binding ability of site I markedly decreased after the operation of an artificial heart-lung machine in all patients, and the binding ability of site II unexpectedly increased in some patients. The variation in pseudopatient serum was similar to that in the patient sera.
  
  
  CONCLUSIONS
  The difference in the binding ability between sites I and II was due to that the fact that the binding ability of site I is more strongly influenced by HSA level reduction than by [FFA]/[HSA] reduction, whereas the binding ability of site II is more strongly influenced by [FFA]/[HSA] reduction than by HSA level reduction in some patients. Therefore, it may be possible to predict the binding ability of site I by monitoring the HSA level without directly monitoring the free phenytoin fraction (%).
authors.affiliation: 2 Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka - Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Totoribe
authors.forename: Norito
authors.initials: N
authors.lastname: Takamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogata
authors.forename: Jin
authors.initials: J
authors.lastname: Tokunaga
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Kunihide
authors.initials: K
authors.lastname: Nakamura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ieiri
authors.forename: Shun
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D003975:Diazepam / Q000737:chemistry / Q000494:pharmacology; D016903:Drug Monitoring / Q000379:methods; D005112:Extracorporeal Circulation / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006355:Heart-Lung Machine; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D005230:Fatty Acids, Nonesterified; D012709:Serum Albumin; D010672:Phenytoin; D003975:Diazepam