Pharmacokinetic quantification of the exchange of drugs between blood and cerebrospinal fluid in man.

Various parameters which may be useful in quantification of drug transit from blood into CSF and vice versa after a short duration infusion are compared here by recalculating previously published data from our group. Due to the slower entry into and elimination from the CSF compartment as compared to the central compartment, the ratio of drug concentrations in CSF and serum sampled at the same time increase with time after an infusion. Therefore, concentration quotients of simultaneously drawn blood and CSF are inadequate to characterise CSF penetration. The ratio of the areas under the concentration-time curves in a body fluid and serum (AUCbody fluid/AUCs) is an established measure to quantify overall penetration from the central into a peripheral compartment. AUCCSF/AUCs is closely correlated with the quotient of the maximum CSF and serum concentrations (CmaxCSF/CmaxS) (rs = 0.87, n = 42, P < 0.001) and with the rate constant of distribution in CSF (CLin/VCSF) (rs = 0.80, n = 42, P < 0.001). Since CmaxCSF/CmaxS depends on the mode of drug administration, it is suggested that AUCCSF/AUCs be used to quantify overall drug transit into CSF. CLin/VCSF is of use when CSF can only be sampled once, or when the velocity of the transit of a drug into CSF is to be described. The CSF exit rate constant (CLout/VCSF) characterises elimination from CSF independent of the elimination from serum and may be applied to estimate the formation rate of CSF; in the present study it averaged 20 ml/h.