Background Entry of B into brain is significantly increased in the absence of BBB PGP expression, while efflux is not affected (Watchko J et al, Pediatr Res 1997;41:186A). PGP may block the entry of amphipatic compounds, or enhance their efflux. PGP function is inhibited by a number of common drugs. We postulated that pretreatment with such drugs would increase the entry of B into brain. Materials and methods Young adult SPRD rats were anesthetized and pretreated with IV bolus doses of: verapamil (1 mg/kg; n=11), propanolol (0.15 mg/ kg; n=7), ceftriaxone (100 mg/kg; n=7), erythromycin (10 mg/kg; n=6), or rifampin (10 mg/kg; n=6). Controls (n=12) received saline. Ten min after the drug injection the rats received 50 mg/kg B over 5 min. They were sacrificed 5 min after the end of the B infusion. Brain bilirubin was measured by acid chlorform extraction. Results were compared with unpaired t-tests. Results The overall mean serum B concentration for the groups at sacrifice was 554±62 μmol/L (mean±SD). Fortuitously there were significant differences between group mean serum B values. Therefore brain:serum B ratios (x 1000) were calculated for all rats and used in the comparisons. Unbound B concentrations were not significantly different between any groups (overall mean±SD = 36±18 nmol/L). There were significant increases of brain:serum B ratio in all but the erythromycin group (see table; * denotes p<0.05 vs control). Discussion It has long been known that drugs which displace B from its albumin binding will increase brain B influx. Ceftriaxone has been reported to be a displacer of B. However, the lack of difference in unbound B concentrations between the groups suggests that displacement of B did not play a significant role in the present study. These findings show that a number of drugs known to inhibit PGP function will significantly increase the acute influx of B into brain. This further supports the role of PGP in modulating B entry into brain, and also raises new concerns regarding the use of drugs in jaundiced infants.

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