HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strenkoski-Nix, L. C. Articles by Nix, D. E. Search for Related Content PubMed PubMed Citation Articles by Strenkoski-Nix, L. C. Articles by Nix, D. E. Social Bookmarking                   What's this?

Pharmacodynamic Interactions of Ciprofloxacin, Piperacillin, and Piperacillin/Tazobactam in Healthy Volunteers

Alan Forrest, PharmD

Jerome J. Schentag, PharmD

Clinical Pharmacokinetics Laboratory, Millard Fillmore Health System, Buffalo New York

David E. Nix, PharmD

University of Arizona, Tucson, Arizona

Mathematical modeling methods were used to study phamacokinetic and pharmacodynamic interactions of the antimicrobial combinations piperacillin plus ciprofloxcin and piperacillin plus tazobactam. Twelve healthy vounteers received the following treatments: piperacillin (4 g), ciprofloxacin (400 mg), piperacillin (4 g) plus ciprfloxacin (400 mg), and piperacillin (4 g) plus tazobatam (0.5 g), via intravenous infusion in a four-period crosover design. Serum drug concentrations were analyzed by means of high-performance liquid chromatography (HPLC), and inhibitory titers were performed against eight organisms. The pharmacodynamic response (growth or no growth) was modeled for each of the monotherapy courses using a Hill-type model where E_max was 1 (100% probability of no growth [P(NG)]), and EC₅₀ was the concentration associated with a 50% P(NG). For piperacillin plus ciprofloxacin, P(NG) was a function of 1) plasma concetrations for both drugs; 2) EC₅₀ values from the montherapy courses; and 3) theta, an interaction term that accommodates synergy, additivity, or antagonism. For pieracillin/tazobactam, the serum ultrafiltrate area under the inhibitory curve was compared with that of piperacilin alone to determine the benefit of tazobactam. The interaction between piperacillin and ciprofloxacin was aditive. The addition of tazobactam to piperacillin was beneficial against certain organisms. The model developed can be used to evaluate the activity of combination regmens against representative pathogens.

CiteULike

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. J. Montgomery, P. M. Beringer, A. Aminimanizani, S. G. Louie, B. J. Shapiro, R. Jelliffe, and M. A. Gill Population Pharmacokinetics and Use of Monte Carlo Simulation To Evaluate Currently Recommended Dosing Regimens of Ciprofloxacin in Adult Patients with Cystic Fibrosis Antimicrob. Agents Chemother., December 1, 2001; 45(12): 3468 - 3473. [Abstract] [Full Text] [PDF]

				R. M. Schiffelers, G. Storm, M. T. ten Kate, L. E. T. Stearne-Cullen, J. G. den Hollander, H. A. Verbrugh, and I. A. J. M. Bakker-Woudenberg In Vivo Synergistic Interaction of Liposome-Coencapsulated Gentamicin and Ceftazidime J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 369 - 375. [Abstract] [Full Text]