Effects of Piperonyl Butoxide on Drug Metabolism in Rodents and Man

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Abstract
Piperonyl butoxide is a potent inhibitor of microsomal enzyme function in mice, as measured by this compound’s ability to inhibit in vivo antipyrine metabolism and to prolong the actions of pentobarbital and zoxazolamine (Flexin). in rats, however, a very high dose of piperonyl butoxide is needed for inhibition of antipyrine and benzo[a]pyrene metabolism and for potentiation of pentobarbital and zoxazolamine action. Rats require more than a hundredfold higher dose of piperonyl butox ide than mice for inhibiting antipyrine metabolism. Studies in man revealed that oral administration of 0.71 mg of piperonyl butoxide per kilogram of body weight did not influence antipyrine metabolism. Since this dose is considerably greater than the daily exposure of individuals using sprays extensively in enclosed areas, it is unlikely that environmental exposure to piperonyl butoxide inhibits human microsomal enzyme function.