title: Interaction between hydroxyethyl starch and propofol: computational and laboratorial study.
abstract: BACKGROUND
  Hydroxyethyl starch (HES) is one of the most used colloids for intravascular volume replacement during anesthesia.
  
  
  OBJECTIVE
  To investigate the existence of a chemical interaction between HES and the anesthetic propofol by in vitro propofol dosing, computational docking, and examination of a complex between propofol and HES by infrared (IR), ultraviolet (UV), and (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy.
  
  
  METHODS
  Ten samples with human plasma mixed with HES or lactated Ringers (n = 5 for each fluid) were prepared, and the propofol free fraction was quantified until 50 min, using gas chromatography-mass spectrometry. The docking study was performed between HES and propofol and compared with controls. The binding affinities between HES and the small molecules were evaluated by binding free energy approximation (ΔGb, kJ mol(-1)). The IR, UV, and NMR spectra were measured for propofol, HES, and a mixture of both obtained by the kneading method.
  
  
  RESULTS
  Propofol concentrations were significantly lower in the HES samples than in the LR samples (p = .021). The spectroscopic characterization of propofol combined with HES revealed differences in spectra and docking studies reinforced a potential interaction between propofol and HES.
  
  
  CONCLUSIONS
  Propofol and HES form a complex with different physical-bio-chemical behavior than the single drugs, which may be an important drug interaction. Further studies should evaluate its clinical effects.
authors.affiliation: a REQUIMTE, Toxicology, Faculdade de Farmácia da , Universidade do Porto , Rua de Jorge Viterbo Ferreira, 228, Porto , 4050-313 , Portugal .
authors.forename: Aura
authors.initials: A
authors.lastname: Silva
authors.forename: Emília
authors.initials: E
authors.lastname: Sousa
authors.forename: Andreia
authors.initials: A
authors.lastname: Palmeira
authors.forename: Pedro
authors.initials: P
authors.lastname: Amorim
authors.forename: Paula
authors.initials: P
authors.lastname: Guedes de Pinho
authors.forename: David A
authors.initials: DA
authors.lastname: Ferreira
mesh_terms: D018686:Anesthetics, Intravenous / Q000097:blood / Q000737:chemistry*; D004347:Drug Interactions; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000097:blood / Q000737:chemistry*; D062105:Molecular Docking Simulation; D010949:Plasma; D010952:Plasma Substitutes / Q000737:chemistry* / Q000378:metabolism; D015742:Propofol / Q000097:blood / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D018686:Anesthetics, Intravenous; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D015742:Propofol
keywords: hydroxyethyl starch; infrared spectroscopy; magnetic resonance spectroscopy; propofol; ultraviolet spectroscopy