PEGylated Liposomes Loading Palmitoyl Prednisolone for Prolonged Blood Concentration of Prednisolone

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概要

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• We investigated the pharmacokinetic behavior of palmitoyl prednisolone (Pal-PLS) and its liposomes with L-α-distearoylphosphatidylcholine (DSPC) and cholesterol (Chol) with or without L-α-distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000) after their intravenous administration in rats. Pal-PLS rapidly disappeared from the systemic circulation and prednisolone (PLS) was regenerated after the administration of DSPC/Chol liposomes. PEGylated liposomes including DSPE-PEG 2000, however, successfully maintained high blood concentrations of Pal-PLS and PLS. The blood profiles of drugs after the administration of liposomal Pal-PLS were analyzed according to a two-compartment model. The larger content of DSPE-PEG 2000 in DSPC/Chol liposomes showed a lower first order elimination rate constant from the central compartment (Kel) and clearance (CL). The area under the concentration?time curve (AUC) of Pal-PLS and PLS in PEGylated liposomes was larger than DSPC/Chol liposomes. The mean resident time (MRT) of Pal-PLS and PLS was also prolonged by PEGylated liposomes. Although DSPC/Chol liposomes showed a high distribution of Pal-PLS in the liver and spleen, PEGylated liposomes significantly decreased the liver distribution of Pal-PLS. The biliary and urinary excretions of drugs for 240 min after drug administration were less than 1% of the administrated dose in any formulations. In conclusion, PEGylated liposomes, including Pal-PLS, are useful for maintain the PLS concentration in the blood after intravenous administration.

• 社団法人日本薬学会の論文
• 2006-07-01

著者

• Kawabata S

  Second Dep. Of Internal Medicine Nagasaki Univ. School Of Medicine

• 中島 幹夫

  佐賀大学医学部附属病院 手術部

• 中島 幹夫

  佐賀医科大学手術部

• Kamihira Shimeru

  長崎大学 医歯薬学総合研究科臨床検査医学講座

• 上平 憲

  長崎大学臨床検査医学

• 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.

• Kohno Shigeru

  長崎大学医学部歯学部附属病院 薬剤部

• 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.

• Sugahara Yazuyuki

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

• Kawakami Shigeru

  Department Of Drug Delivery Research Graduate School Of Pharmaceutical Sciences Kyoto University

• Kanazawa Shigeo

  公立みつぎ総合病院

• 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 M

  Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry

• Fumoto Shintaro

  京都大学 薬学研究科薬品動態制御学

• Hara Shintaro

  長崎大学 医学部第二内科

• Sasaki H

  Dep. Of Hospital Pharmacy Nagasaki Univ. Hospital

• Nakagawa Hiroo

  Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry

• FUMOTO SHINTARO

  Graduate School of Biomedical Sciences, Nagasaki University

• NAKASHIMA MIKIRO

  Graduate School of Biomedical Sciences, Nagasaki University

• NAKAMURA JUNZO

  Graduate School of Biomedical Sciences, Nagasaki University

• NISHIDA KOYO

  Graduate School of Biomedical Sciences, Nagasaki University

• ICHIKAWA Nobuhiro

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

• TESHIMA Mugen

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

• Sakanaka Koji

  参天製薬奈良研究開発センター

• Ichikawa Nobuhiro

  Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry

• Nakano M

  Department Of Laboratory Medicine Nagasaki University School Of Medicine

• 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

• Shiota H

  Nagasaki Univ. Nagasaki Jpn

• Sasaki Hajime

  Semiconductor Group Mitsubishi Electric Corporation

• Sasaki Hideyuki

  R&d Center Toshiba Corp.

• 上平 憲

  長崎大学医学部臨床検査医学

• Kashiwagi Satsuki

  School Of Pharmaceutical Sciences Nagasaki University

• Sasaki H

  Central Research Laboratories Zeria Pharmaceutical Co. Ltd.

• Sasaki H

  Electrotechnical Laboratory

• Sakanaka Koji

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

• Sasaki H

  Nagasaki Univ. School Of Medicine Nagasaki Jpn

• Nishida Koyo

  Graduate School Of Biomedical Sciences Nagasaki Univ.

• Sasaki Hitoshi

  Department Of Hospital Pharmacy Nagasaki University Hospital

• Fumoto Shintaro

  Graduate School Of Biomedical Sciences Nagasaki Univ.

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