Biodistribution and Pharmacokinetics of O-Palmitoyl Tilisolol, a Lipophilic Prodrug of Tilisolol, after Intravenous Administration in Rats

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概要

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• 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.

• 公益社団法人日本薬学会の論文
• 2002-08-01

著者

• 中島 幹夫

  佐賀大学医学部附属病院 手術部

• Murakami T

  Kyoto Univ. Kyoto

• Sugahara Kazuyuki

  長崎大学 医歯薬学総合研究科臨床検査医学講座

• Kawakami Shigeru

  京都大学 薬学研究科

• Kawakami Shigeru

  Dep. Of Drug Delivery Res. Graduate School Of Pharmaceutical Sciences Kyoto Univ.

• Sugahara Yazuyuki

  長崎大学 医歯薬学総合研究科臨床検査医学講座

• 中村 純三

  Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.

• SAKAEDA Toshiyuki

  Department of Hospital Pharmacy, Kobe University School of Medicine

• Sugahara Yazuyuki

  Dep. Of Lab. Medicine Nagasaki Univ. Graduate School Of Biomedical Sciences Nagasaki Univ. Hospital

• NAKASHIMA Mikiro

  Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry

• SASAKI Hitoshi

  Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry

• Nakamura J

  Faculty Of Pharmaceutical Sciences Nagasaki University

• Nakamura Junzo

  長崎大学 薬

• Nakamura Junzo

  School Of Pharmaceutical Sciences Nagasaki University

• Nishida K

  Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.

• Nakashima M

  Dep. Of Clinical Pharmacy Graduate School Of Biomedical Sciences Nagasaki Univ.

• Nakashima Mikiro

  Department Of Hospital Pharmacy Nagasaki University School Of Medicine

• Sakaeda Toshiyuki

  Department Of Hospital Pharmacy School Of Medicine Kobe University

• Sakaeda Toshiyuki

  筑波大学 人間総合科学研究科

• Murakami T

  National Inst. Advanced Industrial Sci. And Technol. Ibaraki

• Hara Shintaro

  長崎大学 医学部第二内科

• Sasaki H

  Dep. Of Hospital Pharmacy Nagasaki Univ. Hospital

• KITAHARA Takashi

  Department of Hospital Pharmacy, Nagasaki University School of Medicine

• HIRAYAMA Ryu

  Graduate School of Biomedical Sciences, Nagasaki University

• Sakanaka Koji

  参天製薬奈良研究開発センター

• Kitahara Takashi

  花王生物科学研究所

• Tsukahara Kazue

  Global R&d Biological Science Kao Corporation

• Hirayama Ryu

  Graduate School Of Biomedical Sciences Nagasaki University

• Tomonari Masahide

  参天製薬奈良研究開発センター

• Mukai T

  九州大学 大学院薬学研究院

• Mukai Takahiro

  Graduate School Of Pharmaceutical Sciences Kyushu University

• Mukai Takahiro

  京都大学 薬学研究科病態機能分析学

• Mukai Takahiro

  Graduate School Of Medicine Kyoto University

• Nakano M

  Department Of Laboratory Medicine Nagasaki University School Of Medicine

• Hirai Masami

  Department Of Applied Biological Chemistry Graduate School Of Agricultural And Life Sciences The Uni

• Hirai Masami

  Department Of Hospital Pharmacy Nagasaki University School Of Medicine

• Mori Tomohiko

  Institute Of Biomaterials And Bioengineering Tokyo Medical And Dental University

• Sasaki Hitoshi

  長崎大学 医歯学部病院薬剤部

• Sasaki Hitoshi

  Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University

• Sakaeda Toshiyuki

  Department Of Hospital Pharmacy Kobe University Hospital

• KAWAKAMI Shigeru

  School of Pharmaceutical Sciences, Nagasaki University

• NISHIDA Koyo

  School of Pharmaceutical Sciences, Nagasaki University

• HIRAYAMA Ryu

  School of Pharmaceutical Sciences, Nagasaki University

• MUKAI Takahiro

  School of Pharmaceutical Sciences, Nagasaki University

• KITAHARA Takashi

  Kao Corporation Biological Science Laboratories

• OHSHIMA Nao

  Department of Hospital Pharmacy, Nagasaki University School of Medicine

• Sakanaka Koji

  Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry:santen Pharma

• Mukuno Takashi

  The Graduate School Of National Science And Technology Okayama University

• Kitahara Takashi

  Department Of Breast Surgery Cancer Institute Hospital

• Ohshima N

  Department Of Hospital Pharmacy Nagasaki University School Of Medicine

• Tsukahara Kazue

  Biological Science Laboratories Kao Corporation

• Kitahara Takashi

  Biological Science Laboratories Kao Corporation

• Kitahara Takashi

  Department Of Breast Oncology Cancer Institute Hospital Of Japanese Foundation For Cancer Research

• Nakashima Mikiro

  Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University

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