Background: Pantoprazole is a proton pump inhibitor drug mainly used for treating peptic diseases. Adverse effects of pantoprazole in the occasional central nervous system (CNS) include headache, vertigo and sleep disturbances. Data in rats suggest that proton pumps are expressed in the inner ear and in the epithelium of the choroid plexus, which would be a potential target to mediate such proton pump inhibitor effects. Methods: To assess the distribution of pantoprazole into the human CNS despite its low lipophilicity (log p = 0.5), we quantified pantoprazole concentrations by liquid chromatography/tandem mass spectrometry in serum and cerebrospinal fluid retain samples withdrawn simultaneously. Twenty-six sample pairs were obtained from 23 neurological patients with therapeutic administration of pantoprazole prior to sampling. Results: Median (interquartile range) serum concentration of total pantoprazole was 142 ng/ml (30.8-622). Cerebrospinal fluid concentration of total pantoprazole was 2.79 ng/ml (1.59-7.3) and reached 2.0% (1.0-4.5%) of simultaneous serum concentrations. Conclusion: This value corresponds to the unbound fraction of pantoprazole in serum reported previously and indicates that pantoprazole CNS concentrations are high enough to exert some effects on possible CNS targets.

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