PII-007 - EXPERIENCES OF CEREBROSPINAL FLUID COLLECTION, EITHER BY SERIAL SAMPLING OR BY LUMBER PUNCTURES, IN CLINICAL PHARMACOLOGY RESEARCH.

P. Dogterom¹, I. den Daas¹, K. Abd-Elaziz¹, C. Fu², C. Barends³, A. Venema³, T. Absalom³; ¹QPS Netherlands, Groningen, The Netherlands, ²QPS USA, Newark, DE, USA, ³University Medical Center Groningen, Groningen, The Netherlands.

Background: Cerebrospinal fluid (CSF) is a valuable source of information for studying the pharmacodynamics (PD) and pharmacokinetics (PK) of drugs targeting the central nervous system (CNS). The PD and PK are regarded as surrogate measures for the activity or concentrations at the brain targets. During recent years, an increasing number of clinical pharmacology studies were conducted at QPS Netherlands with CSF collection by means of a lumbar puncture (LP) or serially via an indwelling epidural catheter. Here we report our experience to demonstrate the safe use of these methodologies.

Methods: The number of studies in which CSF was collected by LP or serially were identified. For each study, the population, number of subjects, type of collection, the purpose of these collections and procedure related adverse events were recorded.

Results: In total 15 studies were identified in which CSF was collected by LPs (8 studies with 1 to 7 LP’s per subject) or serially (7 studies with a sampling period up to 36 hours). Eleven studies were conducted in healthy subjects (n = 91 subjects) and 4 in Alzheimer’s patients (n = 14 patients). Five studies (1 LP and 4 serial) were conducted for PK reasons only, all other studies for PK and PD. There were no dropouts or longer hospitalization periods required because of reported procedure-related adverse events. The majority of adverse events were back pain and headache. In addition, post-dural puncture headache was rare and resolved with simple analgesics and hydration.

Conclusion: Although invasive in nature, CSF sampling by either LP or serially is a safe and well tolerated methodology and a valuable tool for exploring PD and/or PK characteristics of CNS compounds. Obtained results will facilitate next step for clinical development decisions of the compound of interest.