RATE OF DRUG METABOLISM IN OBESE VOLUNTEERS BEFORE AND DURING STARVATION AND IN AZOTEMIC PATIENTS

The elimination of sulfisoxazole was studied to determine the effects of several clinical states on excretion and metabolism of drugs. Plasma and urine free sulfisoxazole and and urine total sulfisoxazole were measured at intervals after a 2.0-Gm. intravenous dose. Plasma half-life and the rates of metabolism and excretion of free drug were calculated from these values. Six healthy obese volunteers had a range of metabolism rates of 0.052-0.074 hr.-1 and excretion rates of 0.028-0.077 hr.-1. Five of these were studied during a period of starvation ketoacidosis at which time excretion rates were decreased in all and metabolism rates were unchanged. Three of four patients with azotemia had low excretion rates and all had very low metabolism rates for this drug. We conclude that azotemic patients cannot metabolize some drugs at a normal rate and therefore may require lower than customary doses to avoid excessive cumulation. © 1969.