Urinary excretion of D-glucaric acid, an indicator of drug metabolizing enzyme activity, in patients with impaired renal function.

The urinary excretion rate of D-glucaric acid, an in vivo parameter of the activity of drug metabolizing enzymes, has been determined in patients with chronic renal insufficiency (glomerular filtration rate 4.5-80 ml/min/1.73m2). The mean value of 22.3 mu moles/d (SD 7.2; n 28) was almost identical to that of healthy controls (22.1 mu moles/d, SD 7.3; n 22). Thus, no inhibitory or enhancing effect of renal insufficiency could be detected. The ability of this parameter to indicate alterations in the activity of hepatic drug metabolism, even in patients with renal insufficiency, was demonstrated by the increased excretion rate of glucaric acid (107 mu moles/d, SD 43.5; n 8; p less than 0.001) after treatment for 7 days with the enzyme inducer phenobarbital. No significant correlation was found between glucaric acid excretion and sex, age, body weight or body surface in 50 patients. Glucaric acid excretion, therefore, should not be related to the creatinine content of urine samples, since creatinine excretion decreases with severity of renal insufficiency and varies with sex, age, body weight and many other conditions. A single dose of dipyrone (Novalgin¿), a further in vivo indicator of drug metabolism, increased glucaric acid excretion on the same day, but no interference was found after a single dose of cortisol.