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青蒿琥酯与考那苦或氟康唑合用或不合用对健康志愿者心脏的比较影响。

Comparative cardiac effects of antimalarial drug halofantrine with or without concomitant administration of kolanut or fluconazole in healthy volunteers.

机构信息

Department of Pharmacology and Therapeutics, University of Ibadan, Nigeria.

Department of Clinical Pharmacology, University College Hospital, Ibadan, Oyo State, Nigeria.

出版信息

Afr Health Sci. 2023 Mar;23(1):262-269. doi: 10.4314/ahs.v23i1.28.

DOI:10.4314/ahs.v23i1.28
PMID:37545974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10398509/
Abstract

BACKGROUND

There is rekindled interest in the cardiotoxicity of antimalarial medicines. Halofantrine is associated with QT interval prolongation. Fluconazole and kolanut alter the pharmacokinetics of halofantrine.

OBJECTIVES

The study assessed the electrocardiographic changes of concomitant administration of kolanut or fluconazole with halofantrine and the effects on the QTc interval.

METHODS

Eighteen healthy volunteers received a single oral dose of halofantrine, halofantrine with kolanut or halofantrine with fluconazole in a crossover study. Twelve lead electrocardiography (ECG) was performed to measure the PR and QT interval (QTc). Statistical analysis was with SPSS at 5% level of significance.

RESULTS

PR intervals were shortened by halofantrine alone and halofantrine with kolanut (169.29 28.67 to 165.29 28.007 and 172.73 29.843 to 163.00 18.336ms) but was prolonged by halofantrine with fluconazole (177.70 27.394 to 186.59 44.434ms). There was prolongation of QTc (384.76 21.727 to 394.12 21.525; 381.36 22.29 to 388.30 17.26 and 382.35 20.08 to 390.84 21.97) in all the three treatment groups at 6 hours, p>0.05. One subject on halofantrine and fluconazole had QTc >440ms. Pre-treatment PR interval (PR) correlated well with post-treatment PR, and with PR r= 0.519, p= 0.014; r=0.664, p=0.013.

CONCLUSION

Concomitant intake of kolanut with halofantrine was significantly decrease cardiac effect of halofantrine.

摘要

背景

人们对抗疟药物的心脏毒性重新产生了兴趣。卤泛群可导致 QT 间期延长。氟康唑和可乐果改变卤泛群的药代动力学。

目的

本研究评估了同时服用可乐果或氟康唑与卤泛群对心电图变化的影响，以及对 QTc 间期的影响。

方法

18 名健康志愿者进行了一项交叉研究，单次口服卤泛群、卤泛群加可乐果或卤泛群加氟康唑。12 导联心电图（ECG）用于测量 PR 和 QT 间期（QTc）。统计学分析采用 SPSS 软件，以 5%的显著性水平进行。

结果

单独使用卤泛群和卤泛群加可乐果可缩短 PR 间期（169.29 28.67 至 165.29 28.007 和 172.73 29.843 至 163.00 18.336ms），但氟康唑可延长 PR 间期（177.70 27.394 至 186.59 44.434ms）。所有三组治疗组在 6 小时时均出现 QTc 延长（384.76 21.727 至 394.12 21.525；381.36 22.29 至 388.30 17.26 和 382.35 20.08 至 390.84 21.97），p>0.05。有 1 例患者同时服用卤泛群和氟康唑时 QTc>440ms。治疗前的 PR 间期（PR）与治疗后的 PR 呈良好相关性，r=0.519，p=0.014；r=0.664，p=0.013。

结论

同时服用可乐果可显著降低卤泛群的心脏毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/d56e6a45e313/AFHS2301-0262Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/48a3fcc032e0/AFHS2301-0262Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/1cd713ad6cdc/AFHS2301-0262Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/0cfde2497092/AFHS2301-0262Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/f6ab86e1c227/AFHS2301-0262Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/ab8912134012/AFHS2301-0262Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/d56e6a45e313/AFHS2301-0262Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/48a3fcc032e0/AFHS2301-0262Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/1cd713ad6cdc/AFHS2301-0262Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/0cfde2497092/AFHS2301-0262Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/f6ab86e1c227/AFHS2301-0262Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/ab8912134012/AFHS2301-0262Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/069f/10398509/d56e6a45e313/AFHS2301-0262Fig6.jpg

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