Novel pharmacokinetic-pharmacodynamic model for prediction of outcomes with an extended-release formulation of ciprofloxacin.
Antimicrob Agents Chemother
; 48(6): 2061-8, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15155200
ABSTRACT
The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers. The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation. The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma. A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes. A "mixture model" was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment. Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively. The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ciprofloxacina
/
Infecções por Escherichia coli
/
Anti-Infecciosos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos