Enhancement of availability of cloricromene at brain level by a lipophilic prodrug.

The pharmacokinetics of a lipophilic alkylamino acid (LAA) prodrug of cloricromene (AD6), name CLOR-C4, was studied in rat plasma and brain. In particular, we observed that the intraperitoneal administration of CLOR-C4 to rats was able to provide a slight but statistically significant higher concentration of the active drug metabolite (cloricromene acid) in the brain compared with the parent drug administered by the same way. The correlation between pharmacokinetic data and calculated partition (LogP) and brain distribution coefficients (LogBB) supported the hypothesis that the amphiphilic nature of the LAA promoiety could be responsible for a better penetration into the brain, more than the simple increase of lipophilicity gained with respect to the parent drug.