Predicting the Clinical Efficacy of Generic Formulations of Ceftriaxone
| Autor: | G. C. Schito, M.H.J. Keenan |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.drug_class
Cephalosporin Microbial Sensitivity Tests Drug resistance Pharmacology medicine.disease_cause Pneumococcal Infections Pharmacokinetics Risk Factors Drug Resistance Bacterial Streptococcus pneumoniae medicine Humans Pharmacology (medical) Clinical efficacy PK/PD models business.industry Ceftriaxone Models Theoretical Anti-Bacterial Agents Treatment Outcome Infectious Diseases Therapeutic Equivalency Oncology Pharmacodynamics business Monte Carlo Method Forecasting medicine.drug |
| Zdroj: | Journal of Chemotherapy. 17:33-40 |
| ISSN: | 1973-9478 1120-009X |
| DOI: | 10.1179/joc.2005.17.supplement-2.33 |
| Popis: | Time above MIC (T>MIC) is regarded as the best pharmacokinetic/pharmacodynamic (PK/PD) parameter for predicting the clinical efficacy of cephalosporins. The concentration of non-protein-bound proprietary ceftriaxone (Rocephin, Roche) in body fluids exceeds this PK/PD criterion for the treatment of Streptococcus pneumoniae respiratory infections. However, the pharmaceutical quality of several generic products may be inferior to Rocephin. We have calculated the variations in fluid concentrations of 34 generic formulations of ceftriaxone and, by mathematical modelling, the implications for attainment of recommended PK/PD criteria, specifically: Treatment of S. pneumoniae infections based on the time that non-protein-bound ceftriaxone concentration in pleural fluid exceeds the CLSI (NCCLS) breakpoint of 4 mg/L for identification of resistant isolates. Impact upon Monte Carlo simulations in plasma for the treatment of S. pneumoniae infections based on T>MIC for 50% dosing interval. Rocephin exceeded the required PK/PD parameters at the mean and two standard deviation levels in both investigations. In contrast, most generic products failed to achieve required PK/PD levels in both investigations. As a consequence, some generic formulations of ceftriaxone may increase risks of clinical failure and/or emergence of resistant isolates. |
| Databáze: | OpenAIRE |
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