ABSTRACT
Objective:Tacrolimus prolonged-release(PR) formulation is a new once-daily formulation of the calcineurin inhibitor tacrolimus,which is currently used in adult liver or kidney transplant patients,and is also gradually widely used in children with nephrotic syndrome.The present study was undertaken to preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in pediatric nephrotic syndrome recipients.Methods:This single-center open-label prospective study was performed in pediatric nephrotic syndrome recipients.Pharmacokinetic samples were collected from eight pediatric subjects with nephrotic syndrome from Department of Pediatric Nephrology in Peking University First Hospital between June and August 2011.They followed administration of single oral doses of tacrolimus PR formulation at 0.02 mg/kg (n =2),0.05 mg/kg (n =2) and 0.10 mg/kg (n =4).Blood samples were taken before the dose and 1,2,4,6,8,10,12 and 24 h after drug intake.No other medicines or interacting food or drinks were taken during the study period.Blood concentrations were measured using an enzyme multiplied immunoassay technique.Pharmacokinetic analysis was performed using WinNolin Phoenix software Version 6.0 (Pharsight,Cary,NC,USA).Results:The pharmacokinetic data were best described by a non-compartment model.Pharmacokinetic parameters of tacrolimus PR formulation in the 3 ascending doses groups (0.02 mg/kg,0.05 mg/kg and 0.10 mg/kg) were as follows:the maxi mum drug concentrations (Cm=/D) were (1.7 ± 1.0) μg/L,(3.1 ± 1.9) μg/L,(8.0 ± 3.5) μg/L,respectively;Areas under the drug concentration-time curve (AUCo-∞/D) were (47.2 ± 47.1) h · μg/ L,(84.0 ± 13.1) h · μg/L,(175.6 ± 107.1) h · μg/L,respectively;Oral clearance rates were (0.8±0.9) L/(h·kg),(0.4±0.1) L/(h · kg),(1.9 ±1.3) L/(h · kg),respectively;Body weight normalized distribution volumes were (7.0 ± 3.4) L/kg,(12.4 ± 8.4) L/kg and (73.6 ± 68.6) L/kg,respectively.Both mean Cmax normalized level for the administered dose (Cmax/D) and mean AUC0-∞ normalized level for the administered dose (AUC0-∞/D) were higher in the 0.05 mg/kg dosage group than in the 0.02 and 0.10 mg/kg dosage group.There were two peaks in the drug concentrations in every dose group;a primary peak appeared at the end of about 2 h followed by a small secondary peak at h 12,which was more noticeable in the 0.10 mg/kg dose group than in the two lower dosages.Conclusion:The pharmacokinetic characteristics of tacrolimus PR formulation were initially explored in pediatric patients with nephritic syndrome.The data presented form a basis for subsequent larger scale studies on pharmacokinetics of tacrolimus PR formulation in nephritic syndrome children.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the incidence of radiation-induced maxillary malignancy after radiotherapy for head and neck cancer.</p><p><b>METHODS</b>A total of 273 patients who suffered from osteoradionecrosis after radiotherapy for head and neck cancer were evaluated. Among them, 6 patients were presented with carcinoma and sarcoma arising from maxillary area after radiotherapy.</p><p><b>RESULTS</b>Radiation-induced maxillary cancers happened at a rate of 2.2% in the patients with osteoradionecrosis. There were no statistically significant differences in age, sex and the time interval between the radiotherapy and the cancer occurrence.</p><p><b>CONCLUSIONS</b>Radiation-induced malignancy after radiotherapy for head and neck cancer is mainly located in maxilla, presenting as squamous cell carcinoma or sarcoma of the maxillary sinus.</p>