Hepatic Metabolism of Aminopyrine in Patients with Chronic Renal Failure

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Abstract
1. To evaluate potential alterations in hepatic metabolism of drugs occurring in patients with renal insufficiency the fate of aminopyrine was studied in 17 patients with chronic renal failure and in 27 normal subjects. 2. Although patients with chronic renal failure exhibited large variations, their aminopyrine plasma disappearance times (mean 0·62 ± sd 0·24 h−1) were significantly higher than those found in normal subjects (0·30 ± 0·07 h−1, P < 0·002). 3. 14CO2 derived from [dimethylamine-14C]aminopyrine disappeared from breath more rapidly in patients with chronic renal failure and a history of analgesic abuse (0·40 ± 0·04 h−1) than in control subjects (0·22 ± 0·03 h−1, P < 0·01) and in other patients with chronic renal failure (0·24 ± 0·04 h−1). 4. Dialysis treatment and serum creatinine concentrations were not correlated with the rates of aminopyrine metabolism. Two additional patients, however, with combined renal and hepatic disease, exhibited markedly slowed rates of aminopyrine demethylation. 5. Although chronic renal failure by itself might not alter microsomal drug metabolism it is concluded that, in patients with a history of abuse of phenacetin-containing analgesics, marked acceleration in aminopyrine N-demethylation may be observed.