Md. Coleman et Mj. Kuhns, Bioactivation of the cyanide antidote 4-aminopropiophenone (4-PAPP) by human and rat hepatic microsomal enzymes: effect of inhibitors, ENV TOX PH, 7(1), 1999, pp. 75-80
The bioactivation of the cyanide antidote methaemoglobin former 4-aminoprop
iophenone (4-PAPP) was studied using rat and human microsomes. With rat liv
er and NADPH in single and two-compartment systems, dapsone and benzocaine
were more potent methaemoglobin generators compared with 4-PAPP. In the sin
gle compartment studies, the order of potency of inhibition of 4-PAPP-media
ted methaemoglobin formation was cimetidine (1.5 mM) > isoniazid (500 mu M)
/diethyldithiocarbamate (DDC, I mM) > erythromycin (500 mu M). Human liver
microsomal activation of 4-PAPP in the two-compartment system was partially
inhibited by both DDC and cimetidine. These preliminary studies suggest th
at 4-PAPP may be metabolised by CYP 2C11, 2E1 and 3A in the rat and CYP 2C,
2E1 and probably 3A4 in man. (C) 1999 Published by Elsevier Science B.V. A
ll rights reserved.