摘要：The purpose of this study was to modify the biodistribution and pharmacokinetics of tilisolol, a β-blocker, using the palmitoyl prodrug approach. After intravenous administration of tilisolol and O -palmitoyl tilisolol in rats, drug concentrations were determined in blood, bile, urine, and several tissues. The concentration-time profiles of tilisolol and O -palmitoyl tilisolol were analyzed pharmacokinetically. The blood concentrations of O -palmitoyl tilisolol after intravenous administration of O -palmitoyl tilisolol were about 10-fold higher than those of tilisolol after intravenous administration of tilisolol. The biliary excretion rates of O -palmitoyl tilisolol and tilisolol after intravenous administration of O -palmitoyl tilisolol were about 10- to 100-fold larger than those of tilisolol after intravenous administration of tilisolol. In addition, the hepatic uptake clearance of O -palmitoyl tilisolol after intravenous administration of O -palmitoyl tilisolol was 3.6-fold higher than that of tilisolol after the intravenous administration of tilisolol. In the in vitro experiments, it was demonstrated that the distribution ratios between blood cells and plasma (blood/plasma) of O -palmitoyl tilisolol and tilisolol was 95.7 and 55.5%, respectively. These findings suggest that O -palmitoyl tilisolol exists as a binding form with biological components, especially blood cells, in systemic circulation. In conclusion, the palmitoyl prodrug approach is useful as a drug delivery system to deliver the parent drug to the liver.
