Population pharmacokinetics and dosing optimization of azlocillin in neonates with early-onset sepsis: a real-world study.

OBJECTIVES: Nowadays, real-world data can be used to improve currently available dosing guidelines and to support regulatory approval of drugs for use in neonates by overcoming practical and ethical hurdles. This proof-of-concept study aimed to assess the population pharmacokinetics of azlocillin in neonates using real-world data, to make subsequent dose recommendations and to test these in neonates with early-onset sepsis (EOS). METHODS: This prospective, open-label, investigator-initiated study of azlocillin in neonates with EOS was conducted using an adaptive two-step design. First, a maturational pharmacokinetic-pharmacodynamic model of azlocillin was developed, using an empirical dosing regimen combined with opportunistic samples resulting from waste material. Second, a Phase II clinical trial (ClinicalTrials.gov: NCT03932123) of this newly developed model-based dosing regimen of azlocillin was conducted to assure optimized target attainment [free drug concentration above MIC during 70% of the dosing interval ('70% fT>MIC')] and to investigate the tolerance and safety in neonates. RESULTS: A one-compartment model with first-order elimination, using 167 azlocillin concentrations from 95 neonates (31.7-41.6 weeks postmenstrual age), incorporating current weight and renal maturation, fitted the data best. For the second step, 45 neonates (30.3-41.3 weeks postmenstrual age) were subsequently included to investigate target attainment, tolerance and safety of the pharmacokinetic-pharmacodynamic model-based dose regimen (100 mg/kg q8h). Forty-three (95.6%) neonates reached their pharmacokinetic target and only two neonates experienced adverse events (feeding intolerance and abnormal liver function), possibly related to azlocillin. CONCLUSIONS: Target attainment, tolerance and safety of azlocillin was shown in neonates with EOS using a pharmacokinetic-pharmacodynamic model developed with real-world data.

[Studies on chemical constituents from leaves of Lysidice brevicalyx].

OBJECTIVE: To study the chemical constituents of Lysidice brevicalyx. METHOD: Various chromatographic techniques were used to isolate and purify the constituents such as column chromatography on silica gel, Rp-silica gel, Sephadex LH-20 and HPLC. The structures were elucidated by chemical evidence and spectroscopic methods. RESULT: Seven compounds were isolated from the 95% ethanol extract of the leaves of L. brevicalyx and these compounds were elucidated as 2-0-[1-(3-methylbutyryl)phloroglucin-ol]-beta-D-glucopynanoside (1), 3-beta-D-glucopyranosyloxy-4, 5-dimethoxy-benzoic acid (2), benzyl alcohol O-beta-D-glucopyra noside (3), polydatin (4), quercetin-3-alpha-L-rhamnopyranoside (5), ethyl gallate (6), benzyl 6-O-alpha-L-arabinofurano syl-beta-D-glucopynanoside (7). CONCLUSION: All Compounds were isolated from this plant for the first time. Compounds 2, 3, 5-7 were obtained from this genus for the first time.