title: Economic benefit of a meropenem dosage strategy based on pharmacodynamic concepts.
abstract: The economic benefit of a meropenem dosage strategy based on pharmacodynamic concepts is described. The pharmacodynamics of novel meropenem dosing regimens were compared with FDA-approved regimens by using Monte Carlo simulation with 5000 subjects. Using the meropenem NCCLS-susceptibility breakpoint of 4 micrograms/mL, the percentage of the dosing interval that drug concentration remained above the minimum inhibitory concentration (%t > MIC) was calculated for each regimen. Probability distributions for half-life and volume of distribution using previously published pharmacokinetic data from healthy volunteers were developed. Cost-minimization analysis was performed from the institution's perspective using both drug acquisition and supply costs. Daily costs for the lower dosage regimens were calculated using 2001 average wholesale prices. The mean %t > MIC for meropenem 500 mg administered every six hours (43.91% [95% confidence interval (CI), 36.77-51.46%]) was similar to that of 1000 mg every eight hours (45.77% [95% CI, 40.06-50.69%]). The mean %t > MIC for meropenem 1000 mg administered every six hours (61.02% [95% CI, 54.71-67.43%]) was similar to the regimen of 2000 mg every eight hours (57.77% [95% CI, 51.84-63.76%]). The 500-mg regimen reduced drug costs by $38.64 per day compared with the standard regimen of 1000 mg administered every eight hours. A pharmacodynamically influenced dosage strategy for meropenem resulted in %t > MIC exposure similar to standard regimens and required a lesser amount of the drug, thereby reducing costs without compromising efficacy.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102-5037, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuti
authors.forename: Dana
authors.initials: D
authors.lastname: Maglio
authors.forename: Charles H
authors.initials: CH
authors.lastname: Nightingale
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000191:economics / Q000493:pharmacokinetics; D016527:Drug Costs; D004352:Drug Resistance, Microbial; D017850:Economics, Pharmaceutical; D006207:Half-Life; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D013845:Thienamycins / Q000008:administration & dosage* / Q000191:economics / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000890:Anti-Infective Agents; D013845:Thienamycins; D000077731:Meropenem