Elimination kinetics of mezlocillin in normal and impaired renal function including the effects of dialysis.

The kinetics of 6-[(R)-2-[3-methylsulfonyl-2-oxo-imidazolidine-1-carboxamido]-2-phenyl-acetamido]-penicillanic acid sodium salt (mezlocillin, Baypen) in renal failure were studied in 23 patients, given 5 g as i.v. infusion. Serum half-lives (t1/2) were around 60 min in normal renal function, 90 to 120 min in patients with a creatinine clearance (Clcr) of 30-60 ml/min, 160 to 190 min at a ClCr of 15 to 30 ml/min and 6 to 14 h in patients with a ClCr below 10 ml/min. There was a linear correlation between serum creatinine and t1/2. Peritoneal dialysis reduced t1/2 to 3 to 4 h and during haemodialysis t1/2 was 1.4 to 2 h with a mean extraction ratio of 0.25. Levels in urine were very high, even in advanced renal failure and the recovery rate was around 60% of dose in normal renal function, but less in renal failure, being only 10-20% at a ClCr of less than 10 ml/min. Levels in peritoneal dialysate fluctuated between 20 and 30 microgram/ml for 4 to 6 h after the infusion, falling slowly but still averaging 10 to 15 microgram/ml after 18 h. Dosage regimens are proposed for various situations in impaired renal function.