Zhiping Li

Background: Patent ductus arteriosus (PDA) is a common congenital heart defect in premature infants. Intravenous injection of ibuprofen is used for PDA treatment, but its optimum dose, efficacy, and safety are unclear. Objectives: This meta-analysis aimed to access randomized controlled trials that compared high- or low-dose ibuprofen with a standard dose of ibuprofen for closure of PDA in preterm infants. Methods: The standard search methods of the Cochrane neonatal review group were used to screen ibuprofen versus indomethacin trials. All groups that used ibuprofen in those trials were filtered out. The high-dose group was defined as those using an average dose of ibuprofen greater than or equal to 10 mg/kg in the first three days. Results: We identified 14 studies of good methodological quality comparing ibuprofen to indomethacin trials among neonates. Results showed that high-dose ibuprofen could remarkably raise the closure rate (relative risk = 0.90, 95% CI = [0.81, 1.00], P = 0.04). No significant differences were found in adverse effects, bleeding disorders, or oliguria. The closure rate in neonates with PDA increased with the ibuprofen dosage (R² = 0.9990). The loading dose produced a significant closure rate compared with the low-dose group (relative risk = 1.91, 95% CI = [1.25, 2.92], P = 0.003), with no increase in toxic side effects. Conclusions: Loading dose is a necessary strategy for infants with PDA. A high dose of ibuprofen for PDA closure was more effective than a normal dose of ibuprofen. The side effects in both treatment groups were not significantly different. Given the small sample size and risk of bias in all trials, the tolerability and safety of the dose regimen should be assessed in a large population before considering the use of these doses for PDA. Keywords: Ibuprofen; Indomethacin; Patent Ductus Arteriosus; Premature Infant

Background: Children are recognized as “therapeutic orphan” in many parts of the world, one expression of this is the lack of adequate pediatric labeling information. Some researches have been done to investigate the pediatric labeling condition in the U.S. and other countries, but no national studies had been carried out in China. This survey was conducted aiming to inquire the current situation of pediatric labeling in China.Methods: We investigated 6020 child-applied medicines from 15 representative Chinese hospitals, and analyzed the information according to the dosage forms, therapeutic category, and label information integrity.Results: Among all these medicines, only 238 (3.95%) are pediatric products, the rest are adult formulations with an extended use in children. The major pediatric formulations were injection (45.95%), tablet (23.69%) and capsule (4.93%), respectively. Alimentary tract/ metabolism medicine (24.70%) and infections medicines (20.60%) had the most species . In prescription drugs, only 210 of 5187 (4%) medicines had adequate pediatric labeling information. The main cause of this deficiency was lack of evidence derived from pediatric clinical trials. Conclusion: The dilemma of “therapeutic orphan” requires significant attention. Inadequate labeling information and lack of pediatric clinical trials were two prominent issues in China. It calls for more efforts from pharmaceutical industries, regulatory agencies, and legislature in China to collaborate and find solution to improve the situation.

To evaluate the proportion of inappropriate digoxin level determinations in children at Children’s Hospital of Fudan University. A retrospective analysis of 291 digoxin level determinations in 210 inpatients was performed. Appropriateness criteria were based on existing criteria that were revised using local expert opinion. The main outcome measure was the proportion of digoxin levels assessed as inappropriate by these criteria. Of the 291 digoxin levels, 126 (43.3%) were considered inappropriate and the remaining 165 (56.7%), appropriate. For the majority of the inappropriate determinations timing of blood sampling was incorrect (74.6%); the remaining determinations were done without proper indication. Almost half the digoxin blood level monitoring was assessed as inappropriate, mainly because of incorrect timing of sampling. Interventions to ensure that appropriate indications and procedures for serum digoxin determination in children at the Children’s Hospital of Fudan University are urgently needed, moreover, special criteria need to be made for children in digoxin blood level monitoring. Key words: Digoxin, therapeutic drug monitoring, children, appropriateness.

A bioanalytical method for the quantification of tacrolimus (TAC) on dried blood spots (DBS) using liquid chromatography, electrospray ionization coupled with tandem mass spectrometry (LC‐ESI‐MS/MS) was developed and validated. It involves solvent extraction of a punch disk of DBS followed by liquid–liquid extraction. The analyte and the internal standard (IS, ascomycin) were separated on a phenyl column using an isocratic mobile phase elution at a flow rate of 0.3 mL/min. The assay was linear from 1 to 80 ng/mL. The mean recovery of TAC was 76.6%. Intra‐assay, inter‐assay imprecision and biases were all less than 15%. TAC on DBS was stable for at least 10 days at room temperature, and at least 24 h at 50°C. A chromatographic effect of the filter paper (Whatman 903) was not detected. The volume of blood (15–50 μL) and hematocrit of blood (ranging from 23.2 to 48.6%) did not show a significant influence on detection of TAC concentration by DBS‐LC‐MS/MS. Fifty samples from patients were detected by both DBS‐LC‐MS/MS and microparticle enzyme‐linked immunoassay (MEIA). TAC concentrations measured by DBS‐LC‐MS/MS method tended to be lower than those by MEIA. Copyright © 2012 John Wiley & Sons, Ltd.