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Three patients under treatment with phenacemide for uncontrollable psychomotor epilepsy were found to have greatly increased serum creatinine levels in the absence of elevated blood urea nitrogen (BUN) values or any other evidence of renal disease. Serum creatinine returned promptly to normal after omission of the phenacemide and rose quickly again on resumption. Experiments in rabbits and rats fully reproduced these clinical observations. In vivo and in vitro studies with the drug and its metabolites excluded these as a cause for a spurious analytical finding. Rabbits given phenacemide have a fall in serum and urine creatine, while the corresponding creatine values rise. With the use of a creatininase degradation procedure, it could be proved that the markedly elevated serum level and the increased excretion consist of the creatinine and not of any other substance. An effect of phenacemide on the conversion rate of creatinine to creatinine in the body is a speculative possibility.
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