Piperacillin pharmacokinetics

Dalla Gosta, T., Nolting, A., Rand, K., and Derendorf, H., Pharmacokinetic-pharmacodynamic modeling of the in vitro antiinfective effect of piperacillin-tazobactam combinations, Int.. Clin. Pharmacol. Ther., 35, 426-433,1997. 

Tazobactam, USP. Tazobactam is a penicillanic acid sulfone that is similar in structure to sulbactam. It is a nioK potent /3-lactamase inhibitor than sulbactam and ha.- 3 slightly broader spectrum of activity than clavulanic acid. Ii has very weak antibacterial activity. Tazobactam is available in fixed-dose, injectable combinations with piperacillin, a broad-spectrum penicillin consisting of an 8 I ratio of pipci- acillin sodium to tazobactam sodium by weight and ma-keted under the trade name Zosyn. The pharmacokineticsprotein bound, experience ven little metabolism, and are excreted in active forms in the urine in high concentrations. 

J. G. Zhi, C. H. Nightingale, and R. Quintiliani, Microbial pharmacodynamics of piperacillin in neutropenic mice of systematic infection dne to Pseudomonas aeruginosa. J Pharmacokinet Biopharm 16 355-375 (1988). 

Piperacillin (Pipracil) extends the spectrum of ampicillin to include most strains of P. aeruginosa, Enterobacteri-aceae (non-P-lactamase-producing), many Bacteroides spp., and E. faecalis. In combination with a P-lactamase inhibitor (piperacillin-tazobactam, Zosyn) it has the broadest antibacterial spectrum of the penicillins. Pharmacokinetic... 

The use of piperacillin is reported to be a risk factor for aminoglycoside-associated nephrotoxicity. A reduction in serum aminoglycoside levels can occur if aminoglycosides and penicillins are given together to patients with severe renal impairment. No pharmacokinetic interaction of importance appears to occur with intravenous aminoglycoside and penicillins in those with normal renal function or between aminoglycosides and carbapenems. The serum levels of oral phenoxymethylpenicillin can be halved by oral neomycin. 

In 3 patients receiving long-term haemodialysis piperacillin doubled the clearance of tobramycin 2 mg/kg, and reduced its half-life from 73 to 22 hours." A patient showed a reduction in the half-life of tobramycin from an expected 70 hours to 10.5 hours after being given piperacillin. In contrast one study found that piperacillin or piperacillin/tazobactam did not change the pharmacokinetics of tobramycin in subjects with renal impairment."... 

No interaction was seen in 10 patients given tobramycin with piperacillin, or in another 10 healthy subjects given once daily gentamicin with piperacillin/tazobactam. Only minimal pharmacokinetic changes were seen in 9 healthy subjects given tobramycin with piperacillin/tazobactam, and 18 cystic fibrosis patients (adults and children) given tobramycin with ticarcillin."... 

Other reports suggest that a pharmacokinetic interaction between parenteral aminoglycosides and piperacillin or other penicillins, resulting in reduced levels of aminoglycoside, seems to oeeur in patients with renal impairment. 

Lau A, Lee M, Flascha S, Prasad R, Sharifl R. Effect of piperacillin on tobramycin pharmacokinetics in patients with nmnal renal function. Antimicrob Agents ChemoJrer (1983) 24, 533-7. 

A randomised, crossover study in 9 healthy subjects found that infusions of vancomycin 500 mg and piperacillin 3 g with tazobactam 375 mg had little or no effect on the pharmacokinetics of any of the antibacterials, except that the piperacillin AUC was slightly raised, by about 7%. It was concluded that no dosage adjustments are needed if these drugs are given together. ... 

Iven H, BraschH. Influence of the antibiotics piperacillin, doxycycline, and tobramycin on the pharmacokinetics of methotrexate in rabbits. Cancer ChemoAer Phamacol (i9Z6) 17, 218-22. 

Wong SL, SOrgel F, Kinzig M, Goldberg MR, Kitt MM, Barriere SL. Lack of pharmacokinetic drug interactions following concomitant administration of telavancin with aztreonam or piperacillin/ tazobactam in healthy participants. J Clin Pharmacol 2009 49(7) 816-23. 

Tjandramaga et al. (1978) studied the pharmacokinetics of piperacillin in normal male volunteers (Table VII). A single intravenous bolus in-... 

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