Pharmacokinetics of once daily prolonged-release formulation of tacrolimus in children with primary nephrotic syndrome.

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 maximum drug concentrations (Cmax/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(AUC0-∞/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.

[Key issues of nephron spring surgery for renal neoplasms].

In recent years the incidence of small renal carcinoma is increasing, and nephron sparing surgery(NSS) becomes the mainstream to treat it. NSS is considered based on comprehensive analysis: the imaging examination, systemic evaluation of the patients, and the indications of NSS. There are three common surgical approaches: intraperitoneal approach, retroperitoneal approach and the joint approach. It is recommended to do intraoperative frozen pathology. If the edge is positive, it is better to cut a deeper layer of the tissue around the renal tumor or transform to radical nephrectomy. Attention should also be paid to reduce heat ischemia time, in order to protect renal function and reduce postoperative renal atrophy. In addition, there are some factors, such as the accurate preoperative evaluation of renal function and surgical skill of the doctors, which can reduce the incidence of postoperative complications and improve survival and quality of life.

Reliability of three methods of occlusion classification.

Four orthodontic faculty at one dental school classified 25 dental casts according to the classification systems of Angle, Katz, and the British Incisor Classification. The dental casts were selected from a pool of 350 pretreatment graduate orthodontic cases and were those deemed the most atypical. The results demonstrated that Katz's classification was more reliable than both Angle and the British. Angle's classification was the least reliable of the three methods.