The highly positively charged, cell-penetrating β 3 -octaarginine has been prepared with a radioactive label by acetylation at the N-terminus with a doubly 14 C-labeled acetyl group ( 14 CH 3 &n.bond; 14 CO). With the radioactive compound, an ADME study (Absorption, Distribution, Metabolism, Excretion) was performed in male rats following an intravenous or oral dose of 1 mg/kg. Sampling was carried out after periods ranging from 5 min to 4 d or 7 d for blood/excretia and quantitative whole-body autoradioluminography (QWBA), respectively. After p.o. dosing, no systemic exposure to peptide-related radioactivity was observed, and the dose was completely excreted in the feces within 24 h suggesting the absence of relevant absorption; less than 3% of the i.v. dose was excreted from the animals within 4 d. Blood levels, after i.v. dosing, dropped within 4 d to less than 2% of C max and decreased afterwards only very slowly. No metabolites were observed in the systemic circulation.

 

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