Creatinine metabolism impairment by an anticonvulsant drug, phenacemide

To report two cases of increased true serum creatinine (Scr) without renal failure caused by an anticonvulsant drug, phenacemide, and to discuss the possible mechanisms.

Two patients treated with phenacemide were investigated for markedly increased Scr and decreased creatinine clearance (Clcr) values. Glomerular filtration rates, as determined by 125I-iothalamate clearance, were normal in both patients and analytical interferences with the Jaffé reaction were excluded. After discontinuation of the drug, phenacemide concentrations became undetectable within 2 days but it took 7-14 days for Scr and Clcr to return to normal values.

The Scr increase with phenacemide (120-170 percent) was higher than that reported with cimetidine or trimethoprim (10-40 percent) and could not be explained solely by inhibition of the tubular secretion of creatinine. The hypothesis of an overproduction of creatinine caused by phenacemide was ruled out by experimental studies in rats. Creatinine increase in tissues was lower than that in the serum of rats given phenacemide. In vitro creatinine influx into red blood cells was inhibited in a dose-dependent way by phenacemide.

Increased Scr concentrations in these patients could be related to an inhibition of transport and a decrease in creatinine volume of distribution. Creatinine concentrations should not be considered when dosage adjustments of renally eliminated drugs are being calculated for patients with such metabolic interferences.