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Войти в исследования Journal of gynecologic oncology · 2016
Immunotherapy for human papillomavirus-associated disease and cervical cancer: review of clinical and translational research.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Kang Eun-Hee, Cho Hae-Yeon, Gui Ling, Lee Ga-Yeong, Lee Eon-Bee, Park Seung-Chun
Аннотация
IMPORTANCE: Edwardsiella tarda induces severe systemic infections in olive flounder (Paralichthys olivaceus), requiring long-acting parenteral therapies to ensure optimal antimicrobial exposure. While amoxicillin trihydrate (AMXT) and florfenicol (FFC) are effective monotherapies, the pharmacokinetic-pharmacodynamic (PK-PD) rationale for their combined intramuscular administration remains insufficiently characterized.
OBJECTIVE: To evaluate the PK-PD profile, synergistic activity, and therapeutic efficacy of a fixed-dose intramuscular AMXT-FFC combination against E. tarda in olive flounder.
METHODS: Minimum inhibitory concentration (MIC) and time-kill assays were conducted. Olive flounder were administered amoxicillin (AMX, 10 mg/kg), FFC (10 mg/kg), or their combination (10 + 10 mg/kg) via intramuscular injection. PK parameters were estimated using noncompartmental analysis. PK-PD indices, including %time above MIC (%T > MIC) and area under the concentration-time curve (AUC)/MIC, were calculated based on the combined MIC (0.5 µg/mL). Therapeutic efficacy was assessed using an dose causing 70% mortality challenge model (3.7 × 10⁶ colony-forming units [CFU]/fish).
RESULTS: The AMXT-FFC combination exhibited synergism (ΣFIC = 0.625), achieving a ≥ 3 log₁₀ CFU/mL reduction within 24 h. Co-administration significantly elevated Cmax and prolonged t1/2, reaching 34.12 µg/mL and 33.27 h for AMX, and 31.59 µg/mL and 13.94 h for FFC, respectively. PK-PD integration showed that PK-PD indices met prespecified efficacy targets (AMX: 100% T > MIC; FFC: AUC/MIC = 1,610.82). In vivo, the combination significantly improved survival compared to controls (75% vs. 27.5%; relative percent survival = 65.5%, p < 0.05).
CONCLUSIONS AND RELEVANCE: A single intramuscular administration of the AMXT-FFC combination provides synergistic antibacterial activity, prolongs exposure, and achieves prespecified PK-PD targets under the controlled experimental conditions.
OBJECTIVE: To evaluate the PK-PD profile, synergistic activity, and therapeutic efficacy of a fixed-dose intramuscular AMXT-FFC combination against E. tarda in olive flounder.
METHODS: Minimum inhibitory concentration (MIC) and time-kill assays were conducted. Olive flounder were administered amoxicillin (AMX, 10 mg/kg), FFC (10 mg/kg), or their combination (10 + 10 mg/kg) via intramuscular injection. PK parameters were estimated using noncompartmental analysis. PK-PD indices, including %time above MIC (%T > MIC) and area under the concentration-time curve (AUC)/MIC, were calculated based on the combined MIC (0.5 µg/mL). Therapeutic efficacy was assessed using an dose causing 70% mortality challenge model (3.7 × 10⁶ colony-forming units [CFU]/fish).
RESULTS: The AMXT-FFC combination exhibited synergism (ΣFIC = 0.625), achieving a ≥ 3 log₁₀ CFU/mL reduction within 24 h. Co-administration significantly elevated Cmax and prolonged t1/2, reaching 34.12 µg/mL and 33.27 h for AMX, and 31.59 µg/mL and 13.94 h for FFC, respectively. PK-PD integration showed that PK-PD indices met prespecified efficacy targets (AMX: 100% T > MIC; FFC: AUC/MIC = 1,610.82). In vivo, the combination significantly improved survival compared to controls (75% vs. 27.5%; relative percent survival = 65.5%, p < 0.05).
CONCLUSIONS AND RELEVANCE: A single intramuscular administration of the AMXT-FFC combination provides synergistic antibacterial activity, prolongs exposure, and achieves prespecified PK-PD targets under the controlled experimental conditions.