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年龄、性别和体重指数对接受骨科手术儿童中丁丙诺啡静脉药代动力学的影响。

Influence of Age, Gender and Body Mass Index on Intravenous Pharmacokinetics of Buprenorphine in Children Undergoing Orthopedic Surgery.

作者信息

Rivera-Espinosa Liliana, Vicencio-Rosas Eréndira, Flores-Pérez Carmen, Flores-Pérez Janett, Lares-Asseff Ismael, Gándara Mireles Jesús Alonso, Solorio-López Edelmira, Chávez-Pacheco Juan Luis

机构信息

Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP), CP 04530, Ciudad de México, México.

Coordinación Nacional Programa Institucional de Atención Paliativa (PALIATIVISSSTE), Dirección Médica, ISSSTE, Mexico City, Mexico.

出版信息

Dose Response. 2024 Aug 8;22(3):15593258241266469. doi: 10.1177/15593258241266469. eCollection 2024 Jul-Sep.

DOI:10.1177/15593258241266469
PMID:39132282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11311171/
Abstract

BACKGROUND

Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug.

OBJECTIVE

The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates.

METHODS

Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 μg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson's correlation and/or ANOVA were used for statistical analysis.

RESULTS

Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance.

CONCLUSIONS

The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.

摘要

背景

丁丙诺啡（BPN）是儿科人群中广泛使用的镇痛药，尽管关于该药物的药代动力学和药效学的研究较少。

目的

目的是表征静脉给药后BPN的药代动力学，并分析年龄、性别、体重、身高、体重指数（BMI）和药物相互作用作为协变量的影响。

方法

纳入99名接受区域麻醉、全身麻醉或联合麻醉下骨科手术的2至10岁儿童。根据美国麻醉医师协会身体状况分类进行评估、接受2μg/kg静脉注射BPN的患者被纳入研究。在1至240分钟内采集血液。通过液相色谱-串联质谱法测定药物血浆浓度。使用Monolix 2021R1软件获得群体药代动力学参数。采用Pearson相关性分析和/或方差分析进行统计分析。

结果

年龄与清除率和中央室容积的变化相关，女性与较低的室间清除率相关，而BMI改变清除率、中央室和外周室容积。BPN与芬太尼和地塞米松联合给药会导致清除率降低。

结论

性别、年龄和BMI等协变量与BPN药代动力学参数的增加或减少直接相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/b16187cd0f83/10.1177_15593258241266469-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/ff0b87b672c2/10.1177_15593258241266469-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/3346ca89597f/10.1177_15593258241266469-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/b910a5c162ff/10.1177_15593258241266469-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/b16187cd0f83/10.1177_15593258241266469-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/ff0b87b672c2/10.1177_15593258241266469-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/3346ca89597f/10.1177_15593258241266469-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/b910a5c162ff/10.1177_15593258241266469-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/965d/11311171/b16187cd0f83/10.1177_15593258241266469-fig4.jpg

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