Absorption, First-Pass Metabolism, and Disposition of Itraconazole in Rats
スポンサーリンク
概要
- 論文の詳細を見る
This study examined the pharmacokinetic disposition, oral absorption and hepatic extraction of itraconazole and its active metabolite, hydroxyitraconazole, in rats. After i.v.injection, serum itraconazole concentrations decreased biexponentially, with an average terminal elimination half-life, volume of distribution and systemic clearance of 4.9h, 6.0l/kg and 14.2ml.min.kg, respectively. When given orally, its absorption was low, with a mean absolute bioavailability of 16.6%. The metabolite to parent drug area under the curve (AUC) ratio was higher after oral administration compared with i.v. injection (mean ratio, 2.7 vs. 0.9). The hepatic drug extraction ratio determined after femoral and portal vein administration averaged 18.5%. When hydroxyitraconazole was injected i.v., the elimination half-life, volume of distribution and systemic clearance of itraconazole averaged 10.0h, 2,4l/kg and 3.4ml/min/kg, respectively. The fraction of the systemically available itraconazole that was metabolized to hydroxyitraconazole was 21.0% and 76.0% after i.v. and oral administration, respectively. In summary, this study is the first reporting the hepatic extraction of itraconazole and the i.v. disposition characteristics of hydroxyitraconazole in rats. Itraconazole is a drug with a low hepatic extraction ratio and its systemic clearance appears to be largely accounted for by hepatic metabolism.
- 公益社団法人日本薬学会の論文
- 2000-06-01
著者
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Lee K
College Of Pharmacy Sungkyunkwan University
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Lee Kang
韓国
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YOO Sun
College of Pharmacy, Sungkyunkwan University
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LEE Kang
College of Pharmacy, Sungkyunkwan University
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Jung Ji
College Of Pharmacy Sungkyunkwan University
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Hong Jongki
College of Pharmacy, Kyung Hee University
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Yoo S
College Of Pharmacy Sungkyunkwan University
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Shin Beom
College Of Pharmacy Sungkyunkwan University
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HONG Jongki
Korea Basic Science Institute
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Jung J
College Of Pharmacy Pusan National University
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Yoo Sun
College Of Pharmacy Sungkyunkwan University
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Lee Kang
College Of Pharmacy Sungkyunkwan University
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JUN Hun
College of Pharmacy, Sungkyunkwan University
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KANG Eunhee
College of Pharmacy, Sungkyunkwan University
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LEE Kyu
College of Pharmacy, Sungkyunkwan University
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Kang Eunhee
College Of Pharmacy Sungkyunkwan University
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Lee Kyu
College Of Pharmacy Sungkyunkwan University
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Shin Beom
College Of Pharmacy Catholic University Of Daegu
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