Pharmacokinetic/pharmacodynamic modeling and simulation to determine effective dosage regimens for doripenem.
J Pharm Sci
; 99(5): 2483-91, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-19904828
ABSTRACT
The aim of this study was to obtain information on effective dosage regimens of doripenem by a modeling and simulation approach based on pharmacokinetic (PK)/pharmacodynamic (PD) theory. The PK/PD model we have already developed was modified to explain in vitro bactericidal kinetics of doripenem for several Pseudomonas aeruginosa strains. Time-course profiles of bacterial counts in patients infected with P. aeruginosa were simulated for typical clinical dosage regimens in Japan considering the variability of PK and the patients' backgrounds by a Monte Carlo simulation. Moreover, time-course profiles of probability achieving the criterion (log(CFU/mL) < 0) were predicted for the evaluation of antibacterial efficacy by renal function. The in vitro bacterial profiles at various dosage regimens could be well explained by the PK/PD model. The simulations suggested the dependence of antibacterial efficacy on the frequency of administration, indicating time-dependent antibacterial activity. It was also suggested that 500 mg t.i.d. showed significant bacterial reduction in patients for any degree of renal function and any severities in 2 weeks after the start of treatment. Our approach to simulate time-course profiles of bacterial counts should be useful for determining and examining effective dosage regimens, including the treatment period, in drug development.
Texto completo:
1
Temas:
ECOS
/
Financiamentos_gastos
Bases de dados:
MEDLINE
Assunto principal:
Carbapenêmicos
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Antibacterianos
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Modelos Biológicos
Tipo de estudo:
Health_economic_evaluation
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Prognostic_studies
Idioma:
En
Revista:
J Pharm Sci
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão