Comparison of the pharmacokinetic and pharmacodynamic activity of piperacillin and mezlocillin.
OBJECTIVE
To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ).


METHODS
Open-label, randomized, three-way crossover study.


METHODS
Hartford Hospital Clinical Research Center.


METHODS
Nine healthy volunteers.


METHODS
Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg.


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.


CONCLUSIONS
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.
Sullivan
M C
MC
Department of Pharmacy, Hartford Hospital, Connecticut 06115.
Nightingale
C H
CH
Quintiliani
R
R
Sweeney
K
K
D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008802:Mezlocillin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010878:Piperacillin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D015610:Serum Bactericidal Test; D013211:Staphylococcus aureus / Q000187:drug effects
D008802:Mezlocillin; D010878:Piperacillin