Abstract

A more sensitive and specific method for the assay of probenecid in biological material was devised for the study of the physiological disposition of the drug in man. Probenecid was found to be rapidly and fairly completely absorbed from the human gastrointestinal tract. The half-life, as estimated by rate of plasma level decline, was the same whether the drug was given orally or intravenously. However, considerable variation of rate of metabolism was observed. Each of nine subjects was given 2 g of probenecid or its sodium salt and the half-life was found to range from 4 to 17 hours. Rate of metabolism depended on the dose—the half-life was shorter with 0.5-g doses than with 2-g doses. Only a small fraction of the administered probenecid was excreted in urine as unchanged drug—less than 5% in 24 hours. This finding and the half-life studies indicate that the drug must be transformed to unknown metabolites or conjugates. Renal clearance studies have shown that net tubular reabsorption occurs in normally acid urine, whereas net tubular secretion was demonstrated with alkaline urine at rapid flow rates. Other workers, using dogs, have made similar observations.