Pharmacokinetics and ascitic fluid penetration of piperacillin in cirrhosis

Abstract

The pharmacokinetics of piperacillin were evaluated in seven healthy volunteers, eight cirrhotic patients without ascites and 11 cirrhotic patients with sterile ascites after a single 15-min intravenous infusion of 4 g of the drug. In ascitic patients, piperacillin rapidly entered the peritoneal fluid. Peritoneal concentrations were higher than 10 mg/l from 0.5 to 8 h after the infusion. Disappearance rate of piperacillin was slower in the ascitic fluid than in plasma. The plasma half life of piperacillin was more prolonged in cirrhotic patients that in control subjects. This difference was more marked in ascitic patients for whom half life was twice as high as in volunteers (1.95 versus 0.91 h; P less than 0.01).

Serum β‐lactam concentrations in critically ill patients with cirrhosis: a matched case–control study

“…Some animal models have shown that hepatic metabolism may contribute to up to 15% of the entire TZP elimination . The biliary excretion of piperacillin seems nearly negligible in healthy humans; however, the half‐lives of TZP are approximately 18 and 25%, respectively, higher in patients with cirrhosis than in healthy subjects . Thus, this metabolic pathway may be underestimated, especially in critically ill patients with other factors altering PK.…”

Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and peritoneum of surgery patients, and dosing considerations based on site-specific pharmacodynamic target attainment

“…Shimizu et al [5] measured the concentration of PIP-TAZ (2 g-0.5 g twice daily regimen) in the peritoneal fluid of five patients at 24, 48, and 72 h; however, those authors did not measure plasma concentrations or characterize peritoneal pharmacokinetics. Wittmann et al [11] and Hary et al [12] reported the penetration of PIP alone into the peritoneal fluid, but not that of PIP-TAZ. There have been no previous reports regarding PIP-TAZ concentrations in the peritoneum.…”