Drug-Induced Porphyrin Biosynthesis. VII. Species, Sex, and Developmental Differences in the Generation of Experimental Porphyria

Abstract

The following drugs have been shown to induce hepatic porphyrin accumulation in 5- to 7-weekold chickens: glutethimide, methsuximide, secobarbital, methyprylon, and mephenytoin, Since these drugs are inactive when administered to mice it is clear that a species difference exists in response to these drugs. Administration of 5β-pregnan-3α, 17α-diol-11, 20-dione to 17-day-old chick embryos results in a large increase in δ-aminolevulinic acid synthase (ALA-synthase) activity accompanied by a very small increase in hepatic porphyrin levels. A drug should therefore be screened for its effects on hepatic ALA-synthase activity as well as porphyrin accumulation prior to administration to porphyric patients. Although it has been reported that ALA-synthase activity cannot be induced by drugs in the livers of newborn rats and rabbits, this enzyme is readily induced by drugs in the livers of newborn chickens.