Carbenoxolone does not cross the blood brain barrier: an HPLC study

CBX was found in the blood of the animals, up to 90 minutes post-injection. However, the cerebrospinal fluid concentration of CBX was negligible.Thus, we conclude that, most likely, CBX does not penetrate the blood brain barrier and therefore recommend careful consideration in the manner of administration, when a central effect is desired.Carbenoxolone (CBX), a derivative of 18-glycyrrhetinic acid [1], is a widely used drug which, in addition to being a mineralocorticoid agonist and inhibiting 11-beta hydroxysteroid dehydrogenase [2], also blocks gap junctional communication [these issues nicely reviewed in reference [3]]. There has been an increasing enthusiasm in the use of CBX in studies where gap junctional coupling has to be altered, both in vitro [4-6] and in vivo [7-11]. Some of these in vivo studies attribute a possible effect of CBX in the central nervous system (CNS) of the animals [8,11] after systemic administration, thus assuming CBX crosses the blood brain barrier. However, the only study that suggested that CBX crosses the blood brain barrier is the Jellinck et al. determination of the inhibition of 11-beta-hydrysteroid dehydrogenase in brain after intraperitoneal (i.p.) injections [12].To clarify this issue, we used a detection method based on high performance liquid chromatography (HPLC) [13], and assessed the drug concentration in blood and in cerebrospinal fluid (CSF) samples of adult rats injected intraperitoneally with CBX (50 mg/Kg). While CBX was found in the plasma, its concentration in CSF was insignificant.Following an i.p. injection of CBX (50 mg/Kg), blood samples were taken from the vein in the tail of the animal, and CSF samples collected from the cisterna magna. A total of 16 rats were used in this study. Figure 1 shows the HPLC-determined CBX concentration in the blood samples, at several time points. We note that, in plasma samples, we obtained about 15–20% of the theoretically estimated maximal CBX blood concentration (estimating a