Intrapulmonary penetration of ceftolozane/tazobactam and piperacillin/tazobactam in healthy adult subjects
| Autor: | Keith A. Rodvold, Jennifer A. Huntington, Obiamiwe Umeh, Mark H. Gotfried, Gurudatt Chandorkar |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Microbiology (medical) Tazobactam Time Factors medicine.drug_class Antibiotics Penicillanic Acid Pharmacology Plasma Young Adult Pharmacokinetics Infusion Procedure polycyclic compounds medicine Humans Pharmacology (medical) Piperacillin medicine.diagnostic_test business.industry Middle Aged respiratory system Anti-Bacterial Agents Cephalosporins Human Experimentation Infectious Diseases Bronchoalveolar lavage Piperacillin/tazobactam Female Ceftolozane business Bronchoalveolar Lavage Fluid medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 67:2463-2469 |
| ISSN: | 1460-2091 0305-7453 |
| Popis: | Objectives Appropriate antibiotic exposure at the site of infection is important for clinically effective therapy. This study compared the epithelial lining fluid (ELF) penetration of ceftolozane/tazobactam, which has potent in vitro activity against many Gram-negative pathogens causing nosocomial pneumonia, with that of piperacillin/tazobactam in healthy adult volunteers. Methods In this Phase 1, open-label trial, 51 healthy adult subjects were randomized to receive three doses of either ceftolozane/tazobactam 1.5 g administered every 8 h via a 60 min infusion or piperacillin/tazobactam 4.5 g administered every 6 h via a 30 min infusion. Serial blood samples were obtained for determination of plasma drug concentrations. Bronchoscopy and bronchoalveolar lavage were performed at pre-specified timepoints in five subjects per timepoint in each treatment group to determine the ELF drug concentration. The penetration of individual analytes into the ELF was determined from the ratio of the area under the plasma concentration-time curve in ELF to that in plasma (AUC(ELF)/AUC(plasma)). Results Plasma and ELF concentrations of ceftolozane, piperacillin and tazobactam increased rapidly, reaching maximal concentrations at the end of the infusion. Mean maximum concentration and AUC from time 0 to the end of the dosing interval (AUC(0-τ)) for ceftolozane in ELF were 21.8 mg/L and 75.1 mg·h/L, respectively. Corresponding values for piperacillin were 58.8 mg/L and 94.5 mg·h/L. The ELF/plasma AUC ratio for ceftolozane was 0.48 compared with 0.26 for piperacillin. Conclusion This study demonstrated that ceftolozane penetrated well into the ELF following parenteral administration of ceftolozane/tazobactam. |
| Databáze: | OpenAIRE |
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