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Titolo:
Relationships of the area under the curve/MIC ratio to different integral endpoints of the antimicrobial effect: Gemifloxacin pharmacodynamics in an in vitro dynamic model
Autore:
Firsov, AA; Lubenko, IY; Portnoy, YA; Zinner, SH; Vostrov, SN;
Indirizzi:
Ctr Sci & Technol LekBioTech, Dept Pharmacokinet, Moscow 117246, Russia Ctr Sci & Technol LekBioTech Moscow Russia 117246 Moscow 117246, Russia Harvard Univ, Mt Auburn Hosp, Sch Med, Cambridge, MA 02138 USA Harvard Univ Cambridge MA USA 02138 osp, Sch Med, Cambridge, MA 02138 USA
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 3, volume: 45, anno: 2001,
pagine: 927 - 931
SICI:
0066-4804(200103)45:3<927:ROTAUT>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESCHERICHIA-COLI; PREDICTORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
13
Recensione:
Indirizzi per estratti:
Indirizzo: Firsov, AA Ctr Sci & Technol LekBioTech, Dept Pharmacokinet, 8 Nauchny Proczd, Moscow117246, Russia Ctr Sci & Technol LekBioTech 8 Nauchny Proczd Moscow Russia 117246
Citazione:
A.A. Firsov et al., "Relationships of the area under the curve/MIC ratio to different integral endpoints of the antimicrobial effect: Gemifloxacin pharmacodynamics in an in vitro dynamic model", ANTIM AG CH, 45(3), 2001, pp. 927-931

Abstract

Most integral endpoints of the antimicrobial effect are determined over anarbitrarily chosen time period, such as the dosing interval (tau), regardless of the actual effect duration. Unlike the tau -related endpoints, the intensity of the antimicrobial effect (I-E) does consider its duration-from time zero to the time when bacterial counts on the regrowth curve achieve the same maximal numbers as in the absence of the antimicrobial, To examine the possible impact of this fundamental difference on the relationships of the antimicrobial effect to the ratio of the area under the concentration-time curve (AUC) to the MIG, a clinical isolate of Staphylococcus aureus wasexposed to simulated gemifloxacin pharmacokinetics over a 40-fold range ofAUC/MIC ratios, from 11 to 466 h, In each run, I-E and four tau -related endpoints, including the area under the time-kill curve (AUBC), the area above the curve (AAC), the area between the control growth and time-kill curves (ABBC), and the ABBC related to the area under the control growth curve (AUGC), were calculated for tau = 24 h. Unlike the I-E, which displayed pseudolinear relationships with the AUC/MIC ratio; each tau -related endpoint showed a distinct saturation at potentially therapeutic AUC/MIC ratios (116 to 466 h) when the antimicrobial effect persisted longer than tau, This saturation results from the underestimation of the true effect and may be eliminated if ABBC, AAC, and AUBC (but not AUGC) are modified and determined inthe same manner as the I-E to consider the actual effect duration, These data suggest a marginal value of the tau -related endpoints as indices of the total antimicrobial effect. Since all of them respond to AUC/MIC ratio changes less than the I-E, the latter is preferable in comparative pharmacodynamic studies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 15:47:44