The pharmacokinetic profile of pipemidic acid was studied in two groups of young healthy volunteers by using a new, sensitive, high-pressure liquid chromatography procedure for quantitation of pipemidic acid in biological fluids. After oral or intravenous administration, the disposition of pipemidic acid may be described as a one- or a two-compartment open model, respectively. Oral bioavailability was 93.1 +/- 11% (mean +/- standard error). After administration of a 100-mg tablet, 13.4 +/- 2.7% was bound to serum proteins at the time of peak drug concentration in serum. Excretion of pipemidic acid in saliva was negligible, the saliva/serum ratio being about 0.32. At steady state after the twice-daily administration of a 500-mg tablet, which is a recommended dosage regimen, a peak drug concentration in serum of 4.3 +/- 0.5 micrograms/ml was attained in 1.2 +/- 0.1 h. The apparent volume of distribution was 1.9 +/- 0.2 liters/kg, and the elimination half-life was 3.4 +/- 0.2 h. The renal clearance was 4.3 +/- 0.7 ml/min per kg, and the total clearance was 6.3 +/- 0.5 ml/min per kg. Despite a considerable water load, the minimum concentration in urine at the end of a dosing interval averaged 100 micrograms/ml, which widely exceeds the known MIC of pipemidic acid against bacteria commonly causing urinary tract infections.