A reference for clinical practice of vancomycin according to pharmacokinetic modeling based on plasma concentration monitoring in children / 中国小儿急救医学

ABSTRACT

Objective To investigate the trough and peak vancomycin plasma concentrations in steady-state following regular dosage and to improve dosing regimen based on pharmacokinetic modeling, providing reference for clinical practice in children.Methods we retrospectively analyzed pharmacokinetics of vancomycin in 50 cases admitted in our PICU who had been confirmed or suspected with gram-positive bacterial infections following regular dosage[40 mg /(kg?d)].Then we tried to optimize dosing regimens with Monte Carlo simulation to evaluate different dosing regimens of vancomycin in children.Results with regular dosage of vancomycin,mean trough concentrations of vancomycin were (1 1.02 ±4.44 )mg /L, trough concentrations higher than 15 mg /L accounted for only 12%.In the actual program,the extension of a single intravenous infusion to 3 hours after administration would result in 26% of trough concentrations dis-tributing in the range above 15 mg /L.If we increased daily dose to 50 mg /kg and 60 mg /kg with simulation, the trough concentration distribution frequency above 15 mg /L would increase from 12% to 32% and 40%. If minimum inhibitory concentration of vancomycin to pathogenic bacteria (Staphylococcus aureus )was 1 mg/L,the probabilities of target attainment for pharmacokinetic/pharmacodynamic evaluation were 51.73%, 76.54% and 87.5% for three dosages [40 mg/(kg?d),50 mg/(kg?d)and 60 mg/(kg?d)]of vancomycin, respectively.we suspected that dosage of 60 mg/(kg?d)was a good choice.with this dosage regimen,we could achieve a substantial increase in the probability of target attainment.Conclusion Following regular dosages, trough concentration distribution frequency from 15 to 20 mg /kg is low.The extension of a single intravenous infusion time can not achieve a good result.According to the result of pathogenic bacteria and anti-microbial susceptibility tests,increasing daily dosage of vancomycin to 60 mg /(kg?d)will help to improve the trough concentration and get more clinic achievements.