Role of the Lipid Emulsion on an Injectable Formulation of Lipophilic KW-3902, a Newly Synthesized Adenosine A1-Receptor Antagonist.
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- Hosokawa Toshihito
- Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
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- Yamauchi Masahiro
- Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
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- Yamamoto Yoshihiko
- Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
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- Iwata Kenji
- Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
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- Mochizuki Harumi
- Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
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- Kato Yasuki
- Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.
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抄録
KW-3902 (a newly synthesized adenosine A1-receptor antagonist) has potent diuretic and renal protective activities. We investigated the influence of the emulsion formulation on the pharmacokinetics of KW-3902 and its metabolite (M1) in rats using three different formulations, i.e., a lipid emulsion about 130 nm in diameter composed of egg yolk lecithin: soybean oil: oleic acid=1 : 1 : 0.048, a liposome about 100 nm in diameter composed of egg yolk lecithin, and a saline solution containing 1% (v/v) each of dimethyl sulfoxide and 1 n NaOH. There was no significant difference in the pharmacokinetic parameters of KW-3902 (elimination half-life (T1/2), area under the plasma concentration–time curves (AUC0—∞), total body clearance (CL), mean residence time (MRT) and volume of distribution at steady-state (Vdss)) and M1 (Cmax, T1/2, AUC0—∞ and MRT) after injection of these three dosage forms. Moreover, we investigated in vitro the binding of KW-3902 to blood components using these three formulations. KW-3902 was completely partitioned into the blood components regardless of its dosage form. These findings suggested that KW-3902 dissociated rapidly from the lipid emulsion or liposome in blood after injection and showed intrinsic pharmacokinetics of KW-3902 at doses of 0.1 and 1 mg/kg. Thus, the lipid emulsion formulation of KW-3902 was defined as a solvent, which was a vehicle for dissolving the drugs to prepare the injection, at its expected effective doses.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 25 (4), 492-498, 2002
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204627727232
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- NII論文ID
- 110003638809
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD38XkslWrsLw%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 6121007
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- PubMed
- 11995931
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可