PMC:7463108 / 107503-108683 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7463108","sourcedb":"PMC","sourceid":"7463108","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7463108","text":"The pharmacokinetic studies above focused on overall systemic exposure of drugs. Plasma concentrations, however, are not always accurate indicators of tissue exposure. Similarly, CNS drug exposure is often estimated based on drug concentrations within the CSF. However, CSF drug levels may not accurately predict brain concentrations. For many drugs with high efflux activities (e.g., substrates of P-gp), CSF tends to over-predict brain tissue concentrations (Liu et al. 2006; Friden et al. 2009; Kodaira et al. 2011, 2014). This could be due, in part, to differential expression of transporters at the blood-CSF barrier vs. BBB. In a study of the ARV drug amprenavir, concentrations of [14C]-amprenavir in CSF versus brain were 23.3 ± 11.2 and 3.33 ± 0.6 nCi/g, respectively, demonstrating overprediction of brain concentrations by CSF (Polli et al. 1999). These studies illustrate the high likelihood of misinterpreting drug brain penetration when using CSF as the surrogate marker. Therefore, direct measurement of brain tissue concentrations in animal models are likely to be more predictive of the interactive effects of ARVs and opioids on ARV and/or opioid brain 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