Abstract
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‐β‐Dp (β: β‐alanine, Dp: N,N‐dimethylaminopropylamide). Py‐Im polyamide (B) was composed of Ac‐PyIm‐β‐ImIm‐PyPy‐β‐PyPy‐β‐Dp. Py‐Im polyamide (C) was composed of Ac‐PyPy‐β‐PyImPy‐PyPyPy‐β‐ImPy‐β‐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 © 2009 John Wiley & Sons, Ltd.