Pharmacokinetics of dapsone and amino acid prodrugs of dapsone

摘要: Amino acid amides of dapsone (DDS), a primary aromatic amine, have been synthesized as water-soluble, chemically stable prodrugs that target peptidase enzymes for cleavage to the parent drug in vivo. The pharmacokinetics DDS, monoacetyldapsone (MADDS; known metabolite), and various L- D-amino derivatives DDS were investigated New Zealand white rabbits after intravenous administration. MADDS exhibit reversible kinetics establish pseudoequilibrium In this study, analytical procedure assayed both MADDS, with formation accounting approximately 25% clearance DDS. L-amino rapidly (t1/2 < 2 min) quantitatively converted administration rabbits. Data are consistent conversion by action stereospecific aminopeptidase suggest they would be good prodrug candidates. corresponding also but half-lives ranged from 30 60 min. specific mechanism is unknown.