Free and bound propofol concentrations in human cerebrospinal fluid

Abstract

Aims The aim of this study was to define the relationship between unbound propofol concentrations in plasma and total drug concentrations in human cerebrospinal fluid (CSF), and to determine whether propofol exists in the CSF in bound form. Methods Forty-three patients (divided into three groups) scheduled for elective intracranial procedures and anaesthetized by propofol target control infusion (TCI) were studied. Blood and CSF samples (taken from the radial artery, and the intraventricular drainage, respectively) from group I (17 patients) were used to investigate the relationship between unbound propofol concentration in plasma and total concentration of the drug in CSF. CSF samples taken from group II (18 patients) were used to confirm the presence of the bound form of propofol in this fluid. The CSF and blood samples taken from group III (eight patients) were used to monitor the course of free and bound CSF propofol concentrations during anaesthesia. Results For group I patients the mean (and 95% confidence interval) total plasma propofol concentration was 6113 (4971, 7255) ng ml -1 , the mean free propofol concentration in plasma was 63 (42, 84) ng ml -1 , and the mean total propofol concentration in CSF was 96 (76, 116) ng ml -1 ( P < 0.05 for the difference between the last two values). For group II patients the fraction of free propofol in CSF was 31 (26, 37)%. For group III patients the fraction of free propofol in CSF during TCI was almost constant (about 36%). Conclusions The unbound propofol concentration in plasma was not equal to its total concentration in CSF and cannot be directly related to the drug concentration in the brain. Binding of propofol to components of the CSF may be an additional mechanism regulating the transport of the drug from blood into CSF.

Cerebrospinal fluid and plasma propofol concentration during total intravenous anaesthesia of patients undergoing elective intracranial tumor removal

“…Therefore there is about 60-fold difference in the concentration of propofol in CSF and in plasma (Engdahl et al, 1998;Dawidowicz et al, 2001b;Dawidowicz et al, 2003a). In contrast to the above founding, the results presented by Dawidowicz et al(2003b) showed that free propofol concentration in blood was lower than the total drug concentration in CSF. Moreover, the unbound CSF propofol percentage in blood is significantly greater than that in blood and is about 30%.…”

Comparison of Pantoprazole Concentrations in Simultaneous Cerebrospinal Fluid and Serum Samples

“…typically only 0.6%), the unbound fraction of pantoprazole in CSF is supposed to be much higher than in serum. This assumption is supported by a study where unbound and total concentrations of another drug, the anaesthetic propofol, were quantified in serum and CSF [6] . Propofol has a molecular weight of 178 Dalton, log p is 3.79, and protein binding is 98% and thus identical to pantoprazole.…”

“…Propofol has a molecular weight of 178 Dalton, log p is 3.79, and protein binding is 98% and thus identical to pantoprazole. In CSF, the unbound fraction of propofol was much higher than in serum and reached about 30% [6] . Thus, it is likely that pantoprazole CNS concentrations are high enough to exert some effects on possible CNS targets.…”

Effects of intraoperative fluid infusions, sample storage time, and sample handling on unbound propofol assay in human blood plasma

“…Hence, our results may prove interesting to clinicists, pharmacologists and analytical chemists alike [6].…”

“…Propofol binds strongly with plasma proteins (97.4-99%) [4][5][6], and due to its effect on the central nervous system, is a potentially dangerous substance. For these reasons it is a good test substance for this research project.…”