Pharmacokinetics of drugs in patients wity the nephrotic syndrome

Abstract

Since the binding of drugs to plasma proteins can significantly alter the intensity of pharmacological and toxicological effects of drugs, we studied the pharmacokinetics of three drugs in patients with hypoalbuminemia secondary to the nephrotic syndrome, but with relatively normal renal function. No significant differences were seen in the pharmacokinetic parameters observed for antipyrine, a drug which is less than 10% bound to plasma proteins. The percentage of unbound diphenylhydantoin, a highly plasma protein bound drug, was found in patients with the nephrotic syndrome to be twice that of healthy individuals (19.2 vs. 10.1%, P<0.001). However, there was also a lower steady state plasma concentration of diphenyl hydantoin (2.9 ± 0.6 vs. 6.8 ± 0.6 μg/ml, P <0.001) secondary to an increase in the plasma clearance (0.048 ± 0.019 vs. 0.022 ± 0.006 liter/kg.h, P<0.001) in the nephrotic patients. The net effect is no difference in the absolute concentration of unbound diphenylhydantoin in healthy individuals (0.69 ± 0.05 μg/ml) and patients with the nephrotic syndrome (0.59 ± 0.06 μg/ml). Qualitatively, similar differences were observed with clofibrate. The dose of these drugs need not be routinely reduced in patients with the nephrotic syndrome as long as they have reasonably normal renal function (creatinine clearance greater than 50 ml/min). With all highly bound acidic drugs, knowledge of the concentration of unbound drug is essential to the proper interpretation of total blood levels and subsequent treatment of the patient. (Journal received: 23 Feb. 1977)