Pharmacokinetics of high doses of piretanide in moderate to severe renal failure.

The pharmacokinetics of piretanide was studied in 10 patients with chronic renal failure. After administration of a high oral dose (12 to 192 mg) of piretanide the kinetics behaved according to an open 2-compartment model. The elimination constant in the first phase (alpha) ranged from 0.385 to 0.756 h-1 and in the second phase (beta) from 0.079 to 0.274 h-1. The corresponding elimination half-lives ranged from 55 to 108 min (t 1/2 alpha) and from 152 to 524 min (t 1/2 beta). Only an average of 2.8% of the orally administered drug was recovered in 24 h urines. Nevertheless, a good correlation was found between urinary recovery or renal clearance of the drug and residual renal function. The elimination of piretanide by non-renal mechanisms appeared to be increased when renal function was greatly diminished.