Quantitation of CSF concentrations and biological activity of probenecid metabolites

The concentrations of probenecid and four of its metabolites have been examined in plasma and CSF by electron capture gas chromatography after extractive methylation. The plasma concentration of each of the metabolites was in the range 1,5-15 micrograms/ml and constituted less than 10% of the parent compound. The penetration into CSF of the metabolites was lower than that of probenecid. The concentration of each of the metabolites was below 0,2 microgram/ml and the total concentration never exceeded 10% of the probenecid concentration. The inhibitory effect of the metabolites on uptake was tested in rabbit renal cortex using 3H-p-amino-hippuric acid. The inhibitory effect was low. From the low activity and relatively low concentrations of the metabolites do not contribute to the probenecid-induced blocking effect of acid transport from the CSF.