Serum protein binding of propofol in patients with renal failure or hepatic cirrhosis.

Abstract

Serum protein binding is a limiting factor in the access of drugs to the central nervous system. Disease-induced modifications of the degree of binding may influence the effect of anesthetic drugs. The protein binding of propofol, an intravenous anaesthetic agent which is highly bound to serum albumin, has been investigated in serum samples from healthy volunteers, from patients with chronic renal failure not undergoing hemodialysis, from patients with chronic renal failure included in a regular hemodialysis program, and from patients with hepatic cirrhosis. Protein binding was determined by the ultrafiltration technique using an Amicon Micropartition System, MPS-1. The percentage of unbound propofol (mean(SD)) in healthy volunteers (n = 16) was 0.98 (0.48) % showing a high interindividual variability. Chronic renal failure did not significantly modify serum protein binding of propofol. In the chronic renal failure group not undergoing regular hemodialysis (n = 9), unbound propofol was 0.92 (0.34) %. In addition, patients in periodic dialysis did not show changes in propofol binding either compared before (1.11 (0.33) %; n = 13) or after hemodialysis (0.87 (0.38) %; n = 12). A slight decrease in albumin concentration was found in all renal patients (P < 0.05) in comparison to healthy volunteers. Creatinine and urea concentrations were higher in these patients (P < 0.01) but in the postdialysis group, the differences in urea levels were not significant when compared with those of volunteers. No changes in the degree of propofol binding were observed in patients with hepatic cirrhosis (0.97 (0.30) %; n = 14) when compared with the group of healthy volunteers. Significant differences were observed in albumin (P < 0.01) and bilirubin (P < 0.05) concentrations. Considering all subjects, the degree of binding did not correlate with biomedical data. Due to the absence of significant changes in the protein binding it is unlikely that there will be an exaggerated pharmacological response in patients with renal and hepatic disease following the administration of a standard propofol dose, although due to interpatient variability careful titration can be recommended.