Pharmacokinetics of creatinine in man and its implications in the monitoring of renal function and in dosage regimen modifications in patients with renal insufficiency

Abstract

A single-compartment model is proposed to describe the pharmacokinetics of creatinine in man. Based on the information from the literature, it was estimated that the average biological half-life of creatinine in normal male adults between 20 to 39 years old is 3.85 hours. This half-life is prolonged in renal patients and becomes 77 hours when renal function decreases to 5 per cent of normal. Based on pharmacokinetic analysis, it was also shown that the time required to reach a new steady-state serum creatinine level after onset of renal failure is highly dependent upon the degree of renal insufficiency. For example, for the subjects analyzed in this paper, it was estimated that it will take 1.1, 2.5, 6.7, and 13.4 days to reach 95 per cent of the steady-state levels when the renal function drops to 50, 25, 10, and 5 per cent of the normal capacity. The model analysis also predicts that from a practical point of view the daily fluctuation in serum level in patients with better than 25 per cent of normal renal function is not very significant. On the other hand, the fluctuation in the early stage of severe renal failure is predicted to be very dramatic. The analysis also predicts that the serum level will decrease to a normal or near normal value within two days after improvement of renal function from moderately to severely impaired state. The data obtained from an anuric patient seems to support the validity of the pharmacokinetic approach used in this study. The implications of the above pharmacokinetic analyses for the monitoring of renal function and dosage regimen modifications in patients with renal insufficiency were discussed.