Effect of cerebrospinal fluid removal on cerebral blood flow and metabolism in the baboon: influence of tyrosine infusion and cerebral embolism on cerebrospinal fluid pressure autoregulation.

Miyakawa, Yuichi; Meyer, John Stirling; Ishihara, Naoki; Nakai, Kenta; Hsu, M C; Deshmukh, Vinod D.

doi:10.1161/01.str.8.3.346

Cited by 7 publications

(2 citation statements)

References 33 publications

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“…By in repeated CSF sampling, however, the constant withdrawal of CSF may influence physiology. This is a concern and must be taken into account [34]. …”

Section: What Methods Are Available To Obtain Information On Unbound mentioning

confidence: 99%

Utility of CSF in translational neuroscience

Lange

2013

J Pharmacokinet Pharmacodyn

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Human cerebrospinal fluid (CSF) sampling is of high value as the only general applicable methodology to obtain information on free drug concentrations in individual human brain. As the ultimate interest is in the free drug concentration at the CNS target site, the question is what CSF concentrations may tell us in that respect. Studies have been performed in rats and other animals for which concentrations in brain extracellular fluid (brain ECF) as a target site for many drugs, have been compared to (cisterna magna) CSF concentrations, at presumed steady state conditions,. The data indicated that CSF drug concentrations provided a rather good indication of, but not a reliable measure for predicting brain ECF concentrations. Furthermore, comparing rat with human CSF concentrations, human CSF concentrations tend to be higher and display much more variability. However, this comparison of CSF concentrations cannot be a direct one, as humans probably had a disease for which CSF was collected in the first place, while the rats were healthy. In order to be able to more accurately predict human brain ECF concentrations, understanding of the complexity of the CNS in terms of intrabrain pharmacokinetic relationships and the influence of CNS disorders on brain pharmacokinetics needs to be increased. This can be achieved by expanding a currently existing preclinically derived physiologically based pharmacokinetic model for brain distribution. This model has been shown to successfully predict data obtained for human lumbar CSF concentrations of acetaminophen which renders trust in the model prediction of human brain ECF concentrations. This model should further evolute by inclusion of influences of drug properties, fluid flows, transporter functionalities and different disease conditions. Finally the model should include measures of target site engagement and CNS effects, to ultimately learn about concentrations that best predict particular target site concentrations, via human CSF concentrations.

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“…By in repeated CSF sampling, however, the constant withdrawal of CSF may influence physiology. This is a concern and must be taken into account [34]. …”

Section: What Methods Are Available To Obtain Information On Unbound mentioning

confidence: 99%

Utility of CSF in translational neuroscience

Lange

2013

J Pharmacokinet Pharmacodyn

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“…Sequential CSF sampling is also possible in humans, although the repeated withdrawal of CSF may negatively influence the physiology. This is a concern and must be taken into account . In rats, it is possible to perform serial CSF sampling through a permanent cannula in the cisterna magna.…”

Section: Advanced Approaches For Studying Bbb Transport and Intrabraimentioning

confidence: 99%

Translational aspects of blood–brain barrier transport and central nervous system effects of drugs: From discovery to patients

Lange

Hammarlund‐Udenaes

2015

Clin Pharma and Therapeutics

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The development of CNS drugs is associated with high failure rates. It is postulated that too much focus has been put on BBB permeability and too little on understanding BBB transport, which is the main limiting factor in drug delivery to the brain. An integrated approach to collecting, understanding, and handling pharmacokinetic-pharmacodynamic information from early discovery stages to the clinic is therefore recommended in order to improve translation to human drug treatment.

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