Elimination kinetics of mezlocillin in normal and impaired renal function including the effects of dialysis
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Abstract:
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.
Insights
Mezlocillin (Baypen) serum half-life significantly increases in renal failure, correlating with creatinine clearance. Dialysis methods reduce mezlocillin half-life, informing dosage adjustments for patients with kidney impairment.
Area of Science:
- Pharmacokinetics
- Nephrology
- Internal Medicine
Background:
- Mezlocillin is a penicillin antibiotic.
- Renal impairment affects drug elimination.
- Understanding mezlocillin kinetics in renal failure is crucial for safe and effective dosing.
Purpose of the Study:
- To investigate the pharmacokinetic profile of mezlocillin in patients with varying degrees of renal function.
- To determine the impact of renal failure and dialysis on mezlocillin's serum half-life and excretion.
- To propose optimized dosage regimens for mezlocillin in patients with impaired renal function.
Main Methods:
- Intravenous administration of 5g mezlocillin to 23 patients.
- Measurement of serum half-life (t1/2) and correlation with creatinine clearance (Clcr).
- Evaluation of mezlocillin kinetics during peritoneal dialysis and hemodialysis.
Main Results:
- Serum half-life of mezlocillin prolonged from ~60 min in normal renal function to 6-14 hours in severe renal failure (Clcr < 10 ml/min).
- A linear correlation was observed between serum creatinine levels and mezlocillin's half-life.
- Peritoneal dialysis reduced t1/2 to 3-4 hours; hemodialysis reduced it to 1.4-2 hours with a 0.25 extraction ratio.
- Urinary recovery of mezlocillin decreased in renal failure, and levels in peritoneal dialysate were significant.
Conclusions:
- Renal function critically influences mezlocillin elimination.
- Dialysis effectively removes mezlocillin, necessitating dose adjustments.
- Proposed dosage regimens can guide mezlocillin use in renal impairment.