British journal of clinical pharmacology · 2026
Oseltamivir drug-disease modelling in infants with influenza virus infection.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Kun, Kimberlin David W, Whitley Richard J, Acosta Edward P, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group
Аннотация
AIMS: Oseltamivir is a commonly used neuraminidase inhibitor for treatment of influenza infection, but little data exist regarding concentration-response relationships.
METHODS: Pharmacokinetic (PK) and viral dynamic data from an earlier NIAID Collaborative Antiviral Study Group trial in paediatric patients with influenza from 0-23 months of age were used to create a PK model linked to an influenza viral dynamic model. Population PK parameters were used to perform broad dose-ranging simulations to determine the oseltamivir carboxylate exposure required to achieve 95% of maximum viral suppression (EC95). PK parameters of interest included the oseltamivir carboxylate steady-state 12-h area-under-the-curve (AUC12) and 12-h trough concentration (C12h). AUC12 and C12h results were related to the time-averaged area under the log10 viral load-time curve from Day 0 to Day 5 minus the baseline viral load (AAUCMB) using a maximum effect model.
RESULTS: A total of 373 plasma samples for oseltamivir and 382 plasma samples for oseltamivir carboxylate from 78 infants were included. The median age and weight at the time of PK sampling were 8 months and 8 kg, respectively. Sixty-two babies with measured influenza viral loads over the course of treatment (12 days, n = 239) were included in the viral dynamic modelling. The modelled EC95 for AUC12 and C12h were 2710 ngxh/mL and 179 ng/mL, respectively.
CONCLUSIONS: Population pharmacokinetic modelling can be directly linked to viral dynamic outcomes and through simulations, dose-ranging studies performed to identify target drug exposures. This approach could be used as a surrogate when concentration-response data do not exist.
METHODS: Pharmacokinetic (PK) and viral dynamic data from an earlier NIAID Collaborative Antiviral Study Group trial in paediatric patients with influenza from 0-23 months of age were used to create a PK model linked to an influenza viral dynamic model. Population PK parameters were used to perform broad dose-ranging simulations to determine the oseltamivir carboxylate exposure required to achieve 95% of maximum viral suppression (EC95). PK parameters of interest included the oseltamivir carboxylate steady-state 12-h area-under-the-curve (AUC12) and 12-h trough concentration (C12h). AUC12 and C12h results were related to the time-averaged area under the log10 viral load-time curve from Day 0 to Day 5 minus the baseline viral load (AAUCMB) using a maximum effect model.
RESULTS: A total of 373 plasma samples for oseltamivir and 382 plasma samples for oseltamivir carboxylate from 78 infants were included. The median age and weight at the time of PK sampling were 8 months and 8 kg, respectively. Sixty-two babies with measured influenza viral loads over the course of treatment (12 days, n = 239) were included in the viral dynamic modelling. The modelled EC95 for AUC12 and C12h were 2710 ngxh/mL and 179 ng/mL, respectively.
CONCLUSIONS: Population pharmacokinetic modelling can be directly linked to viral dynamic outcomes and through simulations, dose-ranging studies performed to identify target drug exposures. This approach could be used as a surrogate when concentration-response data do not exist.