Appearance of pethidine and norpethidine in cerebrospinal fluid of man following intramuscular injection of pethidine.

The plasma and cerebrospinal fluid (CSF) concentrations of pethidine and its main metabolite in plasma, norpethidine, were determined in 20 patients undergoing minor surgery who had received pethidine chloride as premedication in a standard dose of 100 mg intramuscularly. The disposition of pethidine and norpethidine in plasma was followed for 3-8 h after administration. The rate of transfer of the drug and its metabolite from plasma to CSF was assessed on the basis of a single sample of CSF taken from each patient. Pethidine appeared within less than 18 min in the CSF, reaching a maximum after about 90 min. After that, the pethidine concentration ratio CSF/plasma was relatively stable at 0.4-0.5. This is in agreement with the concept that the concentration of a drug in CSF is correlated with the concentration of unbound drug in plasma at equilibrium. Norpethidine which was present in rapidly increasing concentrations in plasma after a delay of 30 min, appeared in CSF in a slower and more erratic fashion as compared to the parent compound. However, after 240 min, the CSF/plasma concentration ratio was similar for pethidine and norpethidine. Thus, transfer from plasma to CSF occurs relatively rapidly. There is little evidence for a functionally significant blood-brain barrier for pethidine and norpethidine.