| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Sign In to gain access to subscriptions and/or personal tools.
|
|
|
|||||||
Sign In to gain access to subscriptions and/or personal tools. |
|||||||||
PHARMACOKINETICS AND PHARMACODYNAMICS |
From the Center for Anti-Infective Research and Development (Dr. Kuti, Dr. Dandekar, Dr. Nightingale, Dr. Nicolau), Research Administration (Dr. Nightingale), and Department of Medicine, Division of Infectious Diseases (Dr. Nicolau), Hartford Hospital, Hartford, Connecticut.
Prolonging the infusion of meropenem over 3 hours increases the percentage of the dosing interval that drug concentrations remain above the minimum inhibitory concentration (MIC), thereby maximizing the pharmacodynamics of this agent and adhering to drug stability constraints. Monte Carlo simulation was employed to determine pharmacodynamic target attainment rates for several prolonged infusion (PI) meropenem dosage regimens as compared with the traditional 30-minute infusion (TI) against Enterobacteriaceae, Acinetobacter species, and Pseudomonas aeruginosa populations. Percent time above the MIC (%T>MIC) exposures for 1000 mg TI q8h, 2000 mg TI q8h, 500 mg PI q8h, 1000 mg PI q12h, 1000 mg PI q8h, 2000 mg PI q12h, and 2000 mg PI q8h were simulated for 10,000 subjects. Variability in pharmacokinetic parameters and MIC distributions were derived from studies in healthy volunteers and the MYSTIC surveillance program, respectively. The probabilities of attaining bacteriostatic (30% T>MIC) and bactericidal (50% T>MIC) exposures were high for all dosage regimens against populations of Enterobacteriaceae. Against Acinetobacter species and Pseudomonas aeruginosa, the 2000-mg PI q8h dosage regimen provided the highest target attainment rates. For mild to moderate infections caused by Enterobacteriaceae, prolonged infusion regimens of 500 mg PI q8h and 1000 mg PI q12h would provide equivalent target attainment rates to the traditional 30-minute infusion while requiring less drug over 24 hours. For more serious infections presumably caused by Acinetobacter species or Pseudomonas aeruginosa, a dose of 2000 mg PI q8h is recommended because of its high bactericidal target attainment rate against these pathogens. Further study of these dosage recommendations in clinical trials is suggested.
Key Words: Meropenem • Monte Carlo simulation • pharmacodynamics • dosage regimens • antimicrobial drug development
Address for reprints: David P. Nicolau, PharmD, FCCP, Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06112.
This article has been cited by other articles:
|
|
 |
|
  A. Y. Peleg, H. Seifert, and D. L. Paterson Acinetobacter baumannii: Emergence of a Successful Pathogen Clin. Microbiol. Rev., July 1, 2008; 21(3): 538 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nomura, N. Morikawa, K. Ikawa, K. Ikeda, Y. Fujimoto, D. Shimizu, K. Taniguchi, K. Shimura, Y. Kanbayashi, T. Komori, et al. Optimized dosage and frequency of cefozopran for patients with febrile neutropenia based on population pharmacokinetic and pharmacodynamic analysis J. Antimicrob. Chemother., April 1, 2008; 61(4): 892 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Rodloff, E. J. C. Goldstein, and A. Torres Two decades of imipenem therapy J. Antimicrob. Chemother., November 1, 2006; 58(5): 916 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. H. Tam, S. Kabbara, R. F. Yeh, and R. H. Leary Impact of Sample Size on the Performance of Multiple-Model Pharmacokinetic Simulations Antimicrob. Agents Chemother., November 1, 2006; 50(11): 3950 - 3952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, J. L. Kuti, C. H. Nightingale, and D. P. Nicolau Population pharmacokinetic analysis and dosing regimen optimization of meropenem in adult patients. J. Clin. Pharmacol., October 1, 2006; 46(10): 1171 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Scheetz, K. M. Hurt, G. A. Noskin, and C. M. Oliphant Applying antimicrobial pharmacodynamics to resistant gram-negative pathogens. Am. J. Health Syst. Pharm., July 15, 2006; 63(14): 1346 - 1360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. H. Tam, S. Adams, M. T. Larocco, L. N. Gerard, L. O. Gentry, and K. W. Garey An integrated pharmacoeconomic approach to antimicrobial formulary decision-making Am. J. Health Syst. Pharm., April 15, 2006; 63(8): 735 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lorente, L. Lorenzo, M. M Martin, A. Jimenez, and M. L Mora Meropenem by Continuous Versus Intermittent Infusion in Ventilator-Associated Pneumonia due to Gram-Negative Bacilli Ann. Pharmacother., February 1, 2006; 40(2): 219 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. A. Krueger, J. Bulitta, M. Kinzig-Schippers, C. Landersdorfer, U. Holzgrabe, K. G. Naber, G. L. Drusano, and F. Sorgel Evaluation by Monte Carlo Simulation of the Pharmacokinetics of Two Doses of Meropenem Administered Intermittently or as a Continuous Infusion in Healthy Volunteers Antimicrob. Agents Chemother., May 1, 2005; 49(5): 1881 - 1889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Cook Pharmacokinetic Alterations of Antimicrobials in the Critically Ill Journal of Pharmacy Practice, April 1, 2005; 18(2): 75 - 83. [Abstract] [PDF]
|
|
|
|
|
|
T. P. Lodise Jr., B. Lomaestro, K. A. Rodvold, L. H. Danziger, and G. L. Drusano Pharmacodynamic Profiling of Piperacillin in the Presence of Tazobactam in Patients through the Use of Population Pharmacokinetic Models and Monte Carlo Simulation Antimicrob. Agents Chemother., December 1, 2004; 48(12): 4718 - 4724. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
