Drug design, development and therapy · 2026
Initial Dosage Optimization of Tacrolimus in Connective Tissue Disease-Associated Interstitial Lung Disease Patients: An Exploratory Study.
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.
Zhang Guan-Ying, Jin Ying-Wei, Wang Jie, Ding Ke-Wen, Zhao Shi-Yuan, Ping Zhi-Hao, Du Jia-Yi, He Su-Mei, Zhang Hai-Bo, Wang Dong-Dong
Аннотация
OBJECTIVE: Tacrolimus has emerged as a promising therapeutic agent for connective tissue disease-associated interstitial lung disease (CTD-ILD) patients. However, its clinical application is substantially hindered by high interindividual pharmacokinetic variability and a narrow therapeutic window, which poses critical challenges particularly for the formulation of the initial dosage regimen.
METHODS: A retrospective real-world study was conducted on 22 CTD-ILD patients receiving tacrolimus therapy. Comprehensive clinical data were systematically collected, encompassing demographic characteristics, routine physiological and biochemical parameters, and detailed concomitant medication records. A population pharmacokinetic (PPK) model for tacrolimus in CTD-ILD patients was developed using the nonlinear mixed-effects modeling approach implemented in NONMEM software. Monte Carlo simulation was subsequently performed to recommend the optimal initial dosage regimen of tacrolimus for CTD-ILD patients.
RESULTS: Based on the results of the model, we proposed initial dosing regimens: for CTD-ILD patients, the recommended initial tacrolimus dosage was 0.10 mg/kg across the body weight range of 50-100 kg, which yielded a target attainment probability of 89.1-93.5%, a probability below 5 ng/mL was 6.3-10.9%, a probability above 10 ng/mL was 0-0.2%.
CONCLUSION: This was an exploratory single-center PPK analysis recommending the initial dosage of tacrolimus for CTD-ILD patients. We proposed the 0.10 mg/kg regimen as a preliminary model-derived starting dose, which warranted prospective validation and therapeutic drug monitoring (TDM). Given the inherent limitations including the relatively small sample size, lack of external validation, further large-scale prospective studies were warranted to confirm these conclusions.
METHODS: A retrospective real-world study was conducted on 22 CTD-ILD patients receiving tacrolimus therapy. Comprehensive clinical data were systematically collected, encompassing demographic characteristics, routine physiological and biochemical parameters, and detailed concomitant medication records. A population pharmacokinetic (PPK) model for tacrolimus in CTD-ILD patients was developed using the nonlinear mixed-effects modeling approach implemented in NONMEM software. Monte Carlo simulation was subsequently performed to recommend the optimal initial dosage regimen of tacrolimus for CTD-ILD patients.
RESULTS: Based on the results of the model, we proposed initial dosing regimens: for CTD-ILD patients, the recommended initial tacrolimus dosage was 0.10 mg/kg across the body weight range of 50-100 kg, which yielded a target attainment probability of 89.1-93.5%, a probability below 5 ng/mL was 6.3-10.9%, a probability above 10 ng/mL was 0-0.2%.
CONCLUSION: This was an exploratory single-center PPK analysis recommending the initial dosage of tacrolimus for CTD-ILD patients. We proposed the 0.10 mg/kg regimen as a preliminary model-derived starting dose, which warranted prospective validation and therapeutic drug monitoring (TDM). Given the inherent limitations including the relatively small sample size, lack of external validation, further large-scale prospective studies were warranted to confirm these conclusions.