'In vitro' binding of propofol to serum lipoproteins in thyroid dysfunction.
OBJECTIVE
To determine a regression relationship between the unbound fraction (fu percent) of propofol, a highly lipophilic intravenous anaesthetic agent, and demographic and biochemical variables in a thyroid dysfunction population.


METHODS
Serum samples from patients with hypo- (n=33) and hyperthyroidism (n=33) and also from healthy volunteers (control group; n=9) were spiked with propofol to a total (bound + unbound propofol) concentration of 10 microg/ml. The unbound concentration was determined using ultrafiltration followed by high-performance liquid chromatography with fluorimetric detection and the unbound fraction percent (fu) and the binding ratio [bound/free concentration (B/F)] were calculated. Albumin, alpha(1)-acid glycoprotein, cholesterol, triglycerides, HDL, LDL, VLDL lipoproteins, and T3 and T4 hormone concentrations were measured. B/F has a linear relationship with lipoprotein concentration--unlike that for fu which is curvilinear - so, we developed a linear regression model of B/F for propofol with the above biochemical variables and with gender.


RESULTS
The fu in hypothyroidism was significantly lower than in the healthy control (mean +/- standard deviation 0.74 +/- 0.13% vs 0.87 +/- 0.12%, P < 0.01) but the fu was no different in hyperthyroid subjects than controls (0.94 +/- 0.16% vs 0.87 +/- 0.12%, P > 0.05). HDL, LDL and VLDL lipoproteins were significant predictors of B/F (P < 0.05) and were capable of explaining 54% of the variability in the 'in vitro' binding of propofol in thyroid disease.


CONCLUSIONS
These results could help explain the interindividual variability in the protein binding of propofol in thyroid dysfunction patients and suggest the inclusion of lipoproteins in covariate model development for the pharmacokinetic/pharmacodynamic parameters of propofol.
de la Fuente
Leire
L
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
Lukas
John C
JC
Vázquez
Jose Antonio
JA
Jauregizar
Nerea
N
Calvo
Rosario
R
Suárez
Elena
E
D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000097:blood* / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood*; D007037:Hypothyroidism / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism; D015742:Propofol / Q000097:blood* / Q000493:pharmacokinetics; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D012737:Sex Factors; D013974:Thyroxine / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D018686:Anesthetics, Intravenous; D001798:Blood Proteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D009961:Orosomucoid; D012709:Serum Albumin; D014280:Triglycerides; D014284:Triiodothyronine; D002784:Cholesterol; D013974:Thyroxine; D015742:Propofol