2009年3月
Pharmacokinetics of Pyrrole-imidazole Polyamides after Intravenous Administration in Rat
BIOPHARMACEUTICS & DRUG DISPOSITION
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- 巻
- 30
- 号
- 2
- 開始ページ
- 81
- 終了ページ
- 89
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/bdd.648
- 出版者・発行元
- JOHN WILEY & SONS LTD
The pharmacokinetics of pyrrole (Py)-imidazole (Im) polyamides was studied in rats after the intravenous administration of these compounds. Py-Im polyamide (A) was composed of Ac-ImPyPy-ImPyPy-beta-Dp (beta: beta-alanine, Dp: N,N-dimethylaminopropylamide). Py-Im polyamide (B) was composed of Ac-PyIm-beta-ImIm-PyPy-beta-PyPy-beta-Dp. Py-Im polyamide (C) was composed of Ac-PyPy-beta-PyImPy-PyPyPy-beta-ImPy-beta-Dp. The molecular weight of Py-Im polyamide (A) was 1035.12, that of Py-Im polyamide (B) was 1422.51 and that of Py-Im polyamide (C) was 1665.78. After the intravenous injection of Py-Im polyamide (A) at 1.3, 2.0, 7.5 and 15.0 mg/kg, Py-Im polyamides (B) and (C) at 1.0, 2.0, 3.0 and 5.0 mg/kg, the average systemic clearance and the volume of distribution at the steady state obtained by a non-compartmental method were in the ranges of 4.6-6.4 ml/min/kg and 244-412 ml/kg, 8.9-10.3 ml/min/kg and 1990-4567 ml/kg, and 7.3-11.9 ml/min/kg and 407-667 ml/kg, respectively. Dose linearity of Py-Im polyamides was observed. The plasma concentration-time profiles after the intravenous administration of Py-Im polyamides (A) and (B) were fitted well by a two-compartment model. Py-Im polyamide (C) was observed at high concentrations in the lungs. The plasma concentration-time profiles after the intravenous administration of Py-Im polyamide (C) were described using a catenary two-compartment model. This model is useful for describing the time course after the administration of high-molecular-weight Py-Im polyamides. Copyright (C) 2009 John Wiley & Sons, Ltd.
- リンク情報
- ID情報
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- DOI : 10.1002/bdd.648
- ISSN : 0142-2782
- PubMed ID : 19226654
- Web of Science ID : WOS:000264219600003