Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China.

AIMS: The aim of the study was to evaluate the suitability of the current caffeine dosing regimen for the Chinese population using modelling and simulation approach. METHODS: Pharmacokinetic samples were collected from 99 Chinese newborns with premature apnoea. The median (range) of gestational age and postmenstrual age were 28.3 (25.0-33.4) weeks and 31.1 (26.4-38.0) weeks, respectively. Newborns were receiving caffeine citrate at a loading dose of 20 mg/kg/d and a maintenance dose of 5-10 mg/kg/d. Caffeine concentrations and CYP1A2 polymorphisms were investigated. Population pharmacokinetic modelling of caffeine in Chinese preterm newborn on a population-wide scale was conducted using NONMEM. RESULTS: A 1-compartment model with first-order elimination was used to describe population pharmacokinetic. With current weight implemented using 0.75 allometric scaling, clearance (CL) was positively related to current weight and postmenstrual age, but a negative relationship was observed with serum creatinine concentration. Eight genotypes of CYP1A2 were tested and none of them had a significant impact on caffeine pharmacokinetic parameters. Interindividual variability of CL and volume of distribution was 7.70 and 65.9%. The median (range) of 95% confidence intervals of CL were 0.0128 (0.0128-0.0131) L/h/kg. Monte Carlo simulation demonstrated that 80% (loading dose) and 98% (maintenance dose) of premature infants treated with a labelled dosing regimen attained the concentration target range of 5-20 mg/L. CONCLUSION: A population PK model of caffeine was developed in Chinese newborns. Body weight-implemented allometric scaling, postmenstrual age and serum creatinine concentration markedly affected caffeine clearance. The labelled dosing regimen is suitable for Chinese premature infants.

[Comprehensive quality control method for total flavonoid of Fructus Aurantii].

OBJECTIVE: To establish a comprehensive quality control method for total flavonoid of Fructus Aurantii. METHODS: RP-HPLC and spectrophotometry were applied for the quantitative and fingerprint analysis of total flavonoid of Fructus Aurantii. The contents of naringin and neohesperidin were determined on an Agilent SB-C18column (4.6 mm × 250 mm, 5 µm). The mobile phase was composed of 0.02 % H3PO4 and CH3CN (80:20). The flow rate was 1 ml/min with DAD detected at 280 nm. The column temperature was maintained at 35°C. The fingerprints were developed on an Agilent SB-C18 column (4.6 mm × 250 mm, 5 µm). The mobile phase was composed of 0.5 % HAc and CH3OH with a linear gradient elution. The ratio of 0.5 % HAc and CH3OH was: 0 min, 80:20; 10 min, 60:40; 35 min, 30:70; 50 min, 0:100. The flow rate was 1 ml/min with DAD detected at 320 nm. The column temperature was maintained at 30 degree. Meanwhile, the contents of total flavonoid were determined at 283 nm. RESULT: The contents range of naringin, neohesperidin and total flavonoid were 38.3 %- 47.2%, 21.0 %- 28.5% and 79.9%-88.6 %, respectively. The fingerprints of the effective fractions showed 12 common peaks and the fingerprint similarity was all above 98.0 % compared with the standard chromatogram. CONCLUSION: The method reported in this paper can be used effectively for the quality control of total flavonoid of Fructus Aurantii.

[GC-MS analysis of volatile oil from the ear of Schizonepeta tenifolia Briq].

Volatile oil was extracted from the ear of Schizonepeta tenifollia Briq. by supercritical carbon dioxide extraction and steam distillation, then GC-MS was used to analyse their components and determine the content. There were 41 components identified from products of supercritical carbon dioxide extraction, while 32 from those of steam distillation. The content of the main component, pulegone, was also different in the two extracts. It showed that the two extractions have differences in component and content to a certain extent.