Metabolism and Excretion of Zosyn (Piperacillin/Tazobactam)
Zosyn undergoes minimal metabolism, with both piperacillin and tazobactam being eliminated primarily unchanged through renal excretion via glomerular filtration and tubular secretion. 1
Piperacillin Metabolism and Excretion
Piperacillin is metabolized to only a minor microbiologically active desethyl metabolite, with the vast majority of the drug remaining unchanged 1
68% of administered piperacillin is excreted unchanged in the urine through both glomerular filtration and tubular secretion 1, 2
Piperacillin and its desethyl metabolite are also secreted into bile, providing a secondary elimination pathway 1
The elimination half-life of piperacillin ranges from 0.7 to 1.2 hours in patients with normal renal function 1
Tazobactam Metabolism and Excretion
Tazobactam is metabolized to a single metabolite (M1) that lacks both pharmacological and antibacterial activity 1
80% of administered tazobactam is eliminated unchanged in the urine, with the remainder excreted as the M1 metabolite 1
Like piperacillin, tazobactam is eliminated primarily by renal excretion through glomerular filtration and tubular secretion 1
Tazobactam and its M1 metabolite are also secreted into bile 1
The elimination half-life of tazobactam is similar to piperacillin, ranging from 0.7 to 1.2 hours 1
Clinical Implications in Renal Impairment
In patients with creatinine clearance below 20 mL/min, the half-life increases twofold for piperacillin and fourfold for tazobactam compared to those with normal renal function 1
Dosage adjustments are required when creatinine clearance falls below 40 mL/min 1
In renal impairment, less tazobactam is excreted renally, resulting in more substrate available for metabolism to M1, while simultaneously the renal elimination of M1 is impaired, leading to increased M1 plasma concentrations 3
Hemodialysis removes 30-40% of piperacillin and tazobactam, with an additional 5% of tazobactam removed as the M1 metabolite 1
Peritoneal dialysis removes approximately 6% of piperacillin and 21% of tazobactam 1
Hepatic Metabolism Considerations
The half-life increases by approximately 25% for piperacillin and 18% for tazobactam in patients with hepatic cirrhosis, though this does not warrant dosage adjustment 1
Unlike drugs that are primarily hepatically metabolized (such as rimantadine, which is 75% metabolized by the liver 4), Zosyn's minimal hepatic metabolism means liver dysfunction has limited impact on drug clearance 1