Background: This study aimed to explore the effects of voriconazole on population pharmacokinetics and optimization of the initial dose of tacrolimus in children with chronic granulomatous disease (CGD) undergoing hematopoietic stem cell transplantation (HSCT).Methods: Thirty-four children with CGD undergoing HSCT were assessed to establish a population pharmacokinetic model (PPM) using the non-linear mixed effect. Tacrolimus concentrations were simulated by the Monte Carlo method in children weighing <25 kg at different doses.Results: In the final model, weight and concomitant use of voriconazole were included as covariates. With the same weight, the relative value of tacrolimus clearance was 1:0.388 in children not taking voriconazole: children taking voriconazole. Compared with children not taking voriconazole, the measured tacrolimus concentrations were all higher in children taking voriconazole (P<0.01); however, these were not corrected by dose or body weight for concentration differences. Thus, we simulated the tacrolimus concentrations using different body weights (5-25 kg) and different dose regimens (0.1-0.8 mg/kg/day) for the same body weight and dose. Tacrolimus concentrations in children taking voriconazole were higher than those in children not taking voriconazole (P<0.01). Also, in children with CGD undergoing HSCT who were not taking voriconazole, the initial dose regimen of 0.5 mg/kg/day was recommended for body weights of 5-10 kg, and 0.4 mg/kg/day was recommended for body weights of 10-25 kg. In children with CGD undergoing HSCT who were taking voriconazole, an initial dose regimen of 0.3 mg/kg/day was recommended for body weights of 5-25 kg.
Conclusions:We established, for the first time, a PPM of tacrolimus in children with CGD undergoing HSCT in which voriconazole significantly increased tacrolimus concentrations. In addition, the initial dose of tacrolimus in children with CGD undergoing HSCT was recommended.
This classification analysis model design includes ultrasound qualitative signs and spleen diameter, which can be detected easily via routine ultrasound without other auxiliary. The classification analysis model is useful in detecting esophageal varices, which may be a supplement for predicting of esophageal varices, and reducing the frequency of endoscopy in the follow-up of cirrhosis patients.
Acute fibrinous and organizing pneumonia (AFOP) is a rare lung disease with distinct histological characteristics that include the diffuse presence of intra-alveolar fibrin, and the absence of eosinophils and hyaline membrane. In the present study, a case of AFOP that was diagnosed by lung biopsy is described. The patient presented with high fever and a cough with expectoration. Computed tomography of the lung showed the presence of bilateral patchy infiltrates, predominantly in the lower lobes. Histopathological examination of lung biopsy from the lower pulmonary lobe confirmed the pathological diagnosis. The patient showed a poor response to treatment with prednisone. Based on a review of literature pertaining to documented AFOP cases, a summary of the clinical features, radiological characteristics, treatment outcomes and prognoses associated with AFOP are presented. The most common pulmonary symptoms included cough, dyspnea and fever. The primary imaging findings in AFOP were consolidation and ground-glass opacity in the bilateral lung.
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