Relationships between total and unbound propofol in plasma and CSF during continuous drug infusion.
BACKGROUND
Propofol is one of the most frequently applied intravenous anesthetics. Although it has been used for a long period, its pharmacokinetics, especially central nervous system pharmacokinetics, are not fully recognized.


OBJECTIVE
Investigation of the relationships between total propofol concentration in blood, total propofol concentration in cerebrospinal fluid (CSF), free propofol concentration in blood, and free anesthetic concentration in CSF in patients undergoing elective neurosurgery and anesthetized with propofol.


METHODS
Eleven patients scheduled for elective intracranial procedures were studied. Propofol was applied in the form of target control infusion. During anesthesia, fractional doses of fentanyl and cisatracurium were administered as necessary. After tracheal intubation the lungs were ventilated to achieve normocapnia with an oxygen-air mixture (Fi O2 = 0.33). CSF and blood were taken at the moment of intraventricular drainage application.


RESULTS
The unbound propofol concentration in plasma is 1.12% (SD 0.61%; SEM 0.18%) of the total concentration in plasma, and the free propofol concentration in plasma is 71.6% (SD 61.0%; SEM 18.4%) of the total CSF propofol concentration. The free anesthetic concentration in CSF is 30.9% (SD 15.7%; SEM 4.7%) of the total CSF propofol concentration, and 61.8% (SD 34.9%; SEM 10.5%) of the free propofol concentration in plasma.


CONCLUSIONS
The relationship between unbound drug concentrations in plasma and in CSF determined in this study leads to the postulate that propofol is transported from blood to CSF by passive diffusion.
Dawidowicz
Andrzej L
AL
Department of Chemical Physics and Physicochemical Separation Methods, Faculty of Chemistry, Maria Curie-Sklodowska University, Lublin, Poland. dawid@hermes.umcs.lublin.pl
Kalitynski
Rafal
R
Fijalkowska
Anna
A
D000328:Adult; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D015742:Propofol / Q000097:blood* / Q000134:cerebrospinal fluid*; D011446:Prospective Studies
D018686:Anesthetics, Intravenous; D015742:Propofol