Serum protein binding of propofol in critically ill patients.
BACKGROUND
Disease-induced modifications in the level of serum proteins may change the degree of binding of drugs highly bound to serum proteins.


METHODS
The serum protein binding of propofol, an intravenous anaesthetic agent was studied in vitro in samples of serum from healthy volunteers (n=28) and from critically ill patients (n=17). The free fraction was obtained by the ultrafiltration technique and was measured by high-performance liquid chromatography. Concentrations of serum albumin, alpha1-acid-glycoprotein and free fatty acids were also measured in all samples.


RESULTS
The percentage of free propofol was significantly increased (P<0.001) in critically ill patients (1.31 (1.06-2.25)%) vs control subjects (1.07 (0.49-1.47)%). Albumin levels were significantly decreased (P<0.001) in patients (16.3 (8.8-24.6) g x l(-1) vs 45.8 (31.4-55.5) g x l[-1]), while levels of alpha1-acid-glycoprotein were increased (P<0.001) (1.9 (0.9-2.8) g x l(-1) vs 0.9 (0.5-1.4) g x l[-1]), as were levels of free fatty acids (0.68 (0.50-1.14) mmol x l(-1) vs 0.37 (0.11-1.05) mmol x l(-1); P<0.05 ). No correlation was found between levels of alpha1-acid-glycoprotein or free fatty acids and the bound/free ratio of propofol. However, a linear relationship was found between levels of albumin and the bound/free ratio (r2=0.25; P<0.001).


CONCLUSIONS
In conclusion, in these critically ill patients, an increase in the percentage of free propofol occurs. The significance of this observation remains uncertain, but may be validated in future studies. However, the observation supports the common idea that potent drugs should be given with great care in critically ill patients.
Zamacona
M K
MK
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Spain.
Suárez
E
E
Aguilera
L
L
Rodríguez-Sasiaín
Aguirre
C
C
Calvo
R
R
D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism; D015742:Propofol / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism
D018686:Anesthetics, Intravenous; D001798:Blood Proteins; D009961:Orosomucoid; D012709:Serum Albumin; D015742:Propofol