STUDY OBJECTIVE: To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ). DESIGN: Open-label, randomized, three-way crossover study. SETTING: Hartford Hospital Clinical Research Center. PATIENTS: Nine healthy volunteers. INTERVENTIONS: Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg. MEASUREMENTS AND MAIN RESULTS: Test organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic analysis revealed that PIP 4 g had 2- to 3-fold higher peak serum bactericidal activity at the end of infusion and 4- to 5-fold higher activity at 0.5 hour than did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ 5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from PIP 4 g remained above the minimum inhibitory concentration of our test strains almost twice as long as MEZ 5 g. CONCLUSION: Since mezlocillin 5 g every 8 hours is currently proving to be effective at many institutions, and since piperacillin 4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we believe that piperacillin 4 g every 8 hours could be used instead, with resulting cost savings.
RCT Entities:
STUDY OBJECTIVE: To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ). DESIGN: Open-label, randomized, three-way crossover study. SETTING: Hartford Hospital Clinical Research Center. PATIENTS: Nine healthy volunteers. INTERVENTIONS: Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg. MEASUREMENTS AND MAIN RESULTS: Test organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic analysis revealed that PIP 4 g had 2- to 3-fold higher peak serum bactericidal activity at the end of infusion and 4- to 5-fold higher activity at 0.5 hour than did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ 5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from PIP 4 g remained above the minimum inhibitory concentration of our test strains almost twice as long as MEZ 5 g. CONCLUSION: Since mezlocillin 5 g every 8 hours is currently proving to be effective at many institutions, and since piperacillin 4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we believe that piperacillin 4 g every 8 hours could be used instead, with resulting cost savings.
Authors: Jürgen B Bulitta; Martina Kinzig; Verena Jakob; Ulrike Holzgrabe; Fritz Sörgel; Nicholas H G Holford Journal: Br J Clin Pharmacol Date: 2010-11 Impact factor: 4.335