Avedissian Sean N, Pham Michelle, Joshi Medha D, Scheetz Marc H, Salamatipour Ashkan, Panickar Jeffin M, Hlukhenka Khrystyna, Miglis Cristina, Chalkias Athanasios, Xanthos Theodoros
Antiviral Pharmacology Laboratory, Center for Drug Discovery, University of Nebraska Medical Center (UNMC), Omaha, NE 68198, USA.
Department of Pharmacy Practice and Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Pharmaceutics. 2021 Apr 13;13(4):539. doi: 10.3390/pharmaceutics13040539.
While the antiarrhythmic drug amiodarone is commonly used in clinical practice, it has a narrow therapeutic index that can lead to acute overdose. One proposed method to deal with this toxicity is lipid emulsion therapy, which may potentially quench the free amiodarone in blood and prevent its further distribution to target organs and tissues. In this study, we utilize an established swine model to examine the effects of Intralipid™ (IL) administration for acute amiodarone toxicity. A total of 14 pigs received an overdose of intravenous amiodarone. After twenty minutes, half of the pigs ( = 7) received IL while the control group ( = 7) received normal saline. Serum concentrations of amiodarone were then analyzed using a validated high-performance liquid chromatography (HPLC) method. Noncompartmental pharmacokinetic analyses were performed on the observed concentrations. There were no statistical differences in the area under the concentration time curve (6 h) or clearance, but there was a difference in the half-life between the two groups (3.12 vs. 0.85 h, = 0.01). The administration of IL did not statistically change the overall exposure of amiodarone in the blood in the first 6 h; however, trends toward prolonged blood retention in the IL group were seen.
虽然抗心律失常药物胺碘酮在临床实践中常用,但其治疗指数狭窄,可导致急性过量。一种应对这种毒性的提议方法是脂质乳剂疗法,它可能会淬灭血液中的游离胺碘酮,并防止其进一步分布到靶器官和组织。在本研究中,我们利用已建立的猪模型来研究静脉输注英脱利匹特(IL)对急性胺碘酮毒性的影响。总共14头猪接受了过量静脉注射胺碘酮。20分钟后,一半的猪(n = 7)接受IL,而对照组(n = 7)接受生理盐水。然后使用经过验证的高效液相色谱(HPLC)方法分析胺碘酮的血清浓度。对观察到的浓度进行非房室药代动力学分析。两组在浓度-时间曲线下面积(6小时)或清除率方面无统计学差异,但两组间半衰期存在差异(3.12对0.85小时,P = 0.01)。IL的给药在统计学上并未改变胺碘酮在最初6小时内的总体血药暴露量;然而,在IL组中观察到血药滞留时间延长的趋势。