@article{oai:nagasaki-u.repo.nii.ac.jp:00023161,
 author = {Kawakami, Shigeru and Ohshima, Nao and Hirayama, Ryu and Hirai, Masami and Kitahara, Takashi and Sakaeda, Toshiyuki and Mukai, Takahiro and Nishida, Koyo and Nakamura, Junzo and Nakashima, Mikiro and Sasaki, Hitoshi},
 issue = {8},
 journal = {Biological & Pharmaceutical Bulletin},
 month = {Aug},
 note = {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., Biological & Pharmaceutical Bulletin v.25(8) p.1072-1076, 2002},
 pages = {1072--1076},
 title = {Biodistribution and Pharmacokinetics of O-Palmitoyl Tilisolol, a Lipophilic Prodrug of Tilisolol, after Intravenous Administration in Rats},
 volume = {25},
 year = {2002}
}