Interaction between hydroxyethyl starch and propofol: computational and laboratorial study.
BACKGROUND
Hydroxyethyl starch (HES) is one of the most used colloids for intravascular volume replacement during anesthesia.


AIM
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.
['Silva|Aura|A|', 'Sousa|Emília|E|', 'Palmeira|Andreia|A|', 'Amorim|Pedro|P|', 'Guedes de Pinho|Paula|P|', 'Ferreira|David A|DA|']
D018686:Anesthetics, Intravenous D004347:Drug Interactions D006801:Humans D006895:Hydroxyethyl Starch Derivatives D062105:Molecular Docking Simulation D010949:Plasma D010952:Plasma Substitutes D015742:Propofol D066244:Proton Magnetic Resonance Spectroscopy
hydroxyethyl starch propofol infrared spectroscopy magnetic resonance spectroscopy ultraviolet spectroscopy