Central Nervous System

Acquired expertise in HV and/or patients

1. PK in Cerebral Spinal Fluid: When it is unknown whether a drug penetrates the CNS, determination of its presence into the CSF helps in establishing valuable PK/PD relationships. Studies on this nature are difficult to perform for ethical and technical reasons as it is not feasible to collect more than a few samples per subject. Therefore, population based pharmacokinetic approaches describing serum vs. CSF concentrations of the drug, are required, (1).

2. Positron Emission Tomography: A validated approach to obtain data of a NCE at the earlier stage of development is the microdosing concept which involves administration of a sub-pharmacological dose of the test compound to humans. The non invasive nuclear imaging PET in conjunction with 11C or 18F labelling is the method of choice for investigating the kinetic profile of a NCE both in blood and tissues of HV vs. patients administered the labelled drug, (2).

3. Low Resolution Brain Electromagnetic Tomography: With the aim of understanding whether a drug works within the brain, EEG-tomography (LORETA), by combining the high time resolution of the EEG with a source localization method that permits a 3-Dimensional tomography of the brain electrical activity, becomes the technique of choice. Different CNS drugs affect brain structures differently which may be visualized by horizontal, sagittal and coronal slices through the brain regions showing the most significant findings after the drug vs. placebo or by surface-rendered statistical parametric maps, (3).

4. Neuropathic Pain: Phase II studies aimed to treat neuropathic pain have been carried out on NCEs (MAO-B inhibitors and nootropic drugs) administered, according to placebo controlled designs, to patients with neuropathic pain and in HIV patients suffering from antiretroviral treatment induced neuropathy.

References

1) Valle M, Barbanoj MJ, Donner A, Izquierdo I, Herranz U, Klein N, Eichler HG, Muller M, Brunner M. "Access of HTB, main metabolite of triflusal, to cerebrospinal fluid in healthy volunteers". Eur J Clin Pharmacol. (2005), 61, 103-11.

2) Bauer M, Langer O, Dal-Bianco P, Karch R, Brunner M, Abrahim A, Lanzenberger R, Hofmann A, Joukhadar C, Carminati P, Ghirardi O, Piovesan P, Forloni G, Corrado ME, Lods N, Dudczak R, Auff E, Kletter K, Muller M. "A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease". Clin Pharmacol 2006 80(3):216-27.

3) Saletu B, Anderer P, Wolzt M, Nosiska D, Assandri A, Noseda E, Nannipieri F, Saletu-Zyhlarz GM "Double-Blind, Placebo-Controlled, Multiple-Ascending-Dose Study on the Pharmaco-dynamics of ABIO-08/01, a New CNS Drug with Potential Anxiolytic Activity. 2. EEG-Tomography Findings Based on LORETA (Low-Resolution Brain Electromagnetic Tomography)" Neuropsychobiology. 2009 Apr 10;59(2):110-122.

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