TY - JOUR T1 - Pharmacokinetics of dapsone and amino acid prodrugs of dapsone. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 770 LP - 775 VL - 22 IS - 5 AU - N L Pochopin AU - W N Charman AU - V J Stella Y1 - 1994/09/01 UR - http://dmd.aspetjournals.org/content/22/5/770.abstract N2 - 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 of DDS, monoacetyldapsone (MADDS; a known metabolite), and various L- and D-amino acid derivatives of DDS were investigated in New Zealand white rabbits after intravenous administration. DDS and MADDS exhibit reversible kinetics and establish a pseudoequilibrium in vivo. In this study, the analytical procedure assayed for both DDS and MADDS, with formation of MADDS accounting for approximately 25% of the clearance of DDS. The L-amino acid derivatives of DDS were rapidly (t1/2 < 2 min) and quantitatively converted to DDS after intravenous administration to rabbits. Data are consistent with conversion of the L-amino acid amides to DDS by the action of stereospecific aminopeptidase enzymes and suggest that they would be good prodrug candidates. The corresponding D-amino acid derivatives were also quantitatively converted to DDS, but the half-lives ranged from 30 to 60 min. The specific mechanism for conversion of the D-amino acid amides to DDS is unknown. ER -