Cerebrospinal fluid is a biofluid contiguous with brain and spinal cord and a plausible tissue for measuring concentrations of central nervous system drugs and biomarkers. Lumbar puncture enables single timepoint sampling while lumbar catheterization enables repeated collection over a period of time. We report here our experience with the procedural safety of both techniques across two phase 1 studies of ESB1609, a brain penetrant sphingosine-1-phosphate receptor agonist, alongside the technical considerations, opportunities, and challenges of implementation. Across both studies, good quality samples were obtained through lumbar puncture and lumbar catheterization. Mild adverse events of post dural puncture headaches were common among participants undergoing lumbar catheterization and resolved with simple analgesics. Surprisingly we found that blood contamination was absent for single lumbar punctures but was detectable throughout the entire lumbar catheter sampling periods, although levels of hemoglobin were very low. We determined that for certain neurological therapeutics, serial cerebrospinal fluid sampling via lumber catheterization in healthy volunteers can provide informative pharmacokinetic and biomarker data but has a relatively high risk of post dural puncture headache compared to lumbar puncture. Acetaminophen co-administered with caffeine might be considered as first line management for post dural puncture headache in appropriate participants.
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