[Analysis on the effective dosage regimens for meropenem, biapenem and doripenem against P. aeruginosa infection based on pharmacokinetics and pharmacodynamics theory]

Abstract

Recently, PK/PD (pharmacokinetics/pharmacodynamics) analysis for the antimicrobial dosage method became one of the popular categories in chemotherapy and infectious disease societies world wide. Carbapenems are often used for empiric therapy because of its broad-spectrum and activities against microorganisms. PK/PD analysis is well studied in some antibiotics including carbapenems and it is necessary also from the point of view of prevention for emergence of resistant strains. We report the result of the analysis for the effective dosage regimens of meropenem, biapenem and doripenem against Pseudomonas aeruginosa infection based on PK/PD theory with the MIC distributions against the strains isolated from the patients blood at Keio University in 2004 and 2006. The highest target attainment rate for the free drug 40% time above the MIC (40%T > or = MIC) in traditional infusion with the MIC distribution against P. aeruginosa isolated from the patients blood at Keio University Hospital in 2004 was as follows: 90.89% in 500 mg every 6 hours regimen for meropenem, 83.25% in 300 mg every 6 hours regimen for biapenem, 81.73% in 250 mg every 6 hours regimen for doripenem in the approved maximum daily dose for each agent. The highest target attainment rate for the free drug 40%T > or = MIC in prolonged infusion with the MIC distribution against P. aeruginosa isolated from the patients blood at Keio University Hospital in 2004 was as follows: 100% in 500 mg every 6 hours regimen for meropenem, 83.97% in 300 mg every 8 hours regimen for biapenem, 99.98% in 500 mg every 8 hours regimen for doripenem in the maximum daily dose for each agents. The highest target attainment rate for the free drug 40%T > or = MIC in traditional infusion with the MIC distribution against P. aeruginosa isolated from the patients blood at Keio University Hospital in 2006 was as follows: 80.57% in 500 mg dose in every 6 hours regimen for meropenem, 56.70% in 300 mg every 6 hours regimen for biapenem, 69.44% in 250 mg every 6 hours regimen for doripenem in the maximum daily dose for each agent. The highest target attainment rate for the free drug 40%T > or = MIC in prolonged infusion with the MIC distribution against P. aeruginosa isolated from the patients blood at Keio University Hospital in 2006 was as follows: 89.35% in 500 mg every 6 hours regimen for meropenem, 60.84% in 300 mg every 6 hours regimen for biapenem, 82.78% in 500 mg every 8 hours regimen for doripenem in the maximum daily dose for each agent. The target attainment rates for the free drug Css/MIC > or = 1 with continuous infusion were lower than the target attainment rates for the free drug 40%T > or = MIC in the regimens of prolonged infusion intermittent dose regimens in all three agents using both of the MIC distributions against P. aeruginosa in 2004 and 2006. The result of the PK/PD analysis for meropenem, biapenem and doripenem indicated that intermittent dose with prolonged infusion was the best method to obtain higher target attainment rate.