{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:42:43Z","timestamp":1761093763930,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,1,17]],"date-time":"2012-01-17T00:00:00Z","timestamp":1326758400000},"content-version":"vor","delay-in-days":3548,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:p><jats:bold>Study Objective.<\/jats:bold> To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin\u2010tazobactam against commonly encountered pathogens. The regimens compared were piperacillin 4.0 g\u2010tazobactam 0.5 g administered every 8 hours, and piperacillin 3.0 g\u2010tazobactam 0.375 g administered every 6 hours.<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Multiple\u2010dose, open\u2010label, randomized, crossover study.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> Clinical research center at Hartford Hospital.<\/jats:p><jats:p><jats:bold>Subjects.<\/jats:bold> Twelve healthy volunteers.<\/jats:p><jats:p><jats:bold>Intervention.<\/jats:bold> The two dosing regimens for piperacillin\u2010tazobactam were administered intravenously in crossover design. Blood was sampled after the third dose.<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> Drug concentrations were determined by a validated high\u2010performance liquid chromatography assay. The percentage of time above minimum inhibitory concentration (%T&gt;MIC) for piperacillin was calculated for a range of MIC values. The maximum concentration (C<jats:sub>max<\/jats:sub>), area under the concentration\u2010time curve (AUC<jats:sub>0\u2010\u03c4<\/jats:sub>), and total clearance of piperacillin differed significantly between the two study regimens, as did the C<jats:sub>max<\/jats:sub>, AUC<jats:sub>0\u2010\u03c4<\/jats:sub>, volume of distribution, and total clearance of tazobactam (p&lt;0.05). The piperacillin 4.0 g\u2010tazobactam 0.5 g regimen provided 40\u201350% T&gt;MIC for MIC values 8\u201316 \u03bcg\/ml; a similar value for the piperacillin 3.0 g\u2010tazobactam 0.375 g regimen was 16\u201332 \u03bcg\/ml.<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> Although statistically significant differences in the pharmaco\u2010dynamic profile were noted for the regimens, both provide adequate T&gt;MIC against commonly encountered pathogens considered susceptible to piperacillin\u2010tazobactam. However, for treatment of <jats:italic>Pseudomonas aeruginosa<\/jats:italic> infection, combination therapy or higher\u2010dosage regimens (e.g., piperacillin 3.0 g\u2010tazobactam 0.375 g every 4 hours, piperacillin 4.0 g\u2010tazobactam 0.5 g every 6 hours, or continuous\u2010infusion piperacillin 12 g\u2010tazobactam 1.5 g\/day) may be a prudent option when full MIC data are unavailable.<\/jats:p>","DOI":"10.1592\/phco.22.8.569.33209","type":"journal-article","created":{"date-parts":[[2004,5,21]],"date-time":"2004-05-21T11:37:53Z","timestamp":1085139473000},"page":"569-577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Pharmacokinetic and Pharmacodynamic Evaluation of Two Dosing Regimens for 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