Brain-to-blood ratio
The brain-to-blood ratio, or brain–blood ratio, is a statistic in pharmacokinetics defined as the ratio of a drug's brain concentrations relative to its circulating blood concentrations.[1] It is a measure of the ability of a drug to cross the blood–brain barrier and exert effects in the central nervous system.[1]
Determinants of brain-to-blood ratio include physicochemical properties like molecular volume, molecular weight, polar surface area, charge state, hydrogen bonding (related to quantity of nitrogen and oxygen atoms), and hydrophilicity–lipophilicity.[1][2][3] Other factors include plasma protein binding, active transport across the blood–brain barrier either into the brain or out of the brain by membrane transport proteins (transporters), and degree of binding to components of brain tissue.[2][3]
An example of brain-to-blood ratio can be made with beta blockers.[4] The highly lipophilic beta blocker propranolol has a brain-to-blood ratio in humans of 15:1 to 26:1, whereas the hydrophilic beta blocker atenolol is peripherally selective with a blood-to-brain ratio of 0.2:1.[4]
References
[edit]- ^ a b c Nicolazzo JA, Charman SA, Charman WN (March 2006). "Methods to assess drug permeability across the blood-brain barrier". J Pharm Pharmacol. 58 (3): 281–293. doi:10.1211/jpp.58.3.0001. PMID 16536894.
- ^ a b Bickel U (January 2005). "How to measure drug transport across the blood-brain barrier". NeuroRx. 2 (1): 15–26. doi:10.1602/neurorx.2.1.15. PMC 539317. PMID 15717054.
- ^ a b Mangas-Sanjuan V, González-Alvarez M, Gonzalez-Alvarez I, Bermejo M (October 2010). "Drug penetration across the blood-brain barrier: an overview". Ther Deliv. 1 (4): 535–562. doi:10.4155/tde.10.37. PMID 22833966.
- ^ a b Drayer DE (1987). "Lipophilicity, hydrophilicity, and the central nervous system side effects of beta blockers". Pharmacotherapy. 7 (4): 87–91. doi:10.1002/j.1875-9114.1987.tb04029.x. PMID 2891122.