Disposition of amiodarone in rats after single and multiple intra-peritoneal doses

Najjar, Tawfeeg A.

doi:10.1007/bf03192314

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…The increase in phospholipids can be attributed to amiodarone-induced inhibition of phospholipid degradation, a postulate supported by considerable experimental data [8][9][10][11] . The differential tissue effects of amiodarone on phospholipids, namely the absence of an increase in total phospholipid content in the heart compared to the signifi cant changes in other tissues, is consistent with the tissue distribution of the drug, because amiodarone concentrations in lung are approximately fi ve fold greater than that in the heart [27] while the kidney concentrates amiodarone to the same extent as the lung and skeletal muscle is slightly lower than lung [22] . There are little previous data on the effects of amiodarone on cardiac phospholipid content.…”

Section: Effect On Tissue Phospholipids and Their Major Subfractionsmentioning

confidence: 77%

Effect of Amiodarone on Phospholipid Content and Composition in Heart, Lung, Kidney and Skeletal Muscle: Relationship to Alteration of Thyroid Function

Rabkin¹

2006

Pharmacology

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To investigate the effect of chronic amiodarone treatment on tissue phospholipids, a marker of amiodarone-induced toxicity, and to test the hypothesis that tissue phospholipids changes are related to amiodarone-induced effects on thyroid function, male Wistar rats were treated with amiodarone and tissue phospholipid content and fractions were assessed. Twenty-six animals were allocated to 4 groups: (i) group 1 received amiodarone, 20 mg/kg per day, for 3 weeks (n = 6); (ii) group 2 received amiodarone for 5 weeks (n = 6); (iii) group 3 received drug for 6 weeks (n = 6), and (iv) group 4 (control group) received the diluent for 6 weeks (n = 8). Total phospholipid content of lung, kidney and skeletal muscle but not heart was increased after 3 weeks of amiodarone treatment. With longer durations of treatment, the phospholipid content was significantly (p < 0.05) reduced in all four organs. The proportion of phospholipids in different classes was modified by amiodarone treatment with the most consistent changes across different tissues being reductions in phosphatidylethanolamine and increases in phosphatidylserine. Serum thyroxine concentration was significantly (p < 0.05) reduced at 5 weeks of treatment and thereafter. There was a significant correlation between serum thyroxine and total phospholipid concentration in heart (r = 0.555; p < 0.05) and lung (r = 0.502; p < 0.05). For heart, there was a significant correlation between serum thyroxine and the distribution of phospholipid classes, mainly for phosphatidylserine even after considering amiodarone dose. The same was found in the lung. In the kidney and skeletal muscle, there was a significant (p < 0.05) correlation between serum thyroxine and the proportion of phospholipids in phosphatidylcholine and sphingomyelin. In conclusion, this study presents the novel finding of a biphasic tissue phospholipid response to amiodarone characterized by a short term increase in phospholipids in lung, kidney and skeletal muscle but not the heart followed by a long term decline in phospholipids in all four organs that is likely due to a direct action of amiodarone on phospholipid metabolism and potentially the result of amiodarone-induced reduction in thyroid function.

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Section: Effect On Tissue Phospholipids and Their Major Subfractionsmentioning

confidence: 77%

Effect of Amiodarone on Phospholipid Content and Composition in Heart, Lung, Kidney and Skeletal Muscle: Relationship to Alteration of Thyroid Function

Rabkin¹

2006

Pharmacology

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“…14.7 μmol/kg) injection of amiodarone was chosen because, in a similar model of anaesthetized rat [34], intravenous doses above 10 mg/kg were shown to dramatically reduce or totally suppress the occurrence of postischaemic VT, VF and mortality. This dose would lead to a theoretical C 0 of 245 μ m , which would decay in accordance with a t 1/2 close to 50 h [38].…”

Section: Discussionmentioning

confidence: 99%

Effect of two new PBN‐derived phosphorylated nitrones against postischaemic ventricular dysrhythmias

Vergely¹,

Renard²,

Moreau³

et al. 2003

Fundamemntal Clinical Pharma

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Spin traps might exert antioxidant cardioprotective effects during myocardial ischaemia-reperfusion where free radicals are thought to be responsible for the occurrence of reperfusion injury. The aim of our study was to investigate the effects of two new alpha-phenyl N-tert-butylnitrone (PBN)-derived beta-phosphorylated nitrones: 2-N-oxy-N-[benzylidène amino] diéthyl propyl-2-phosphate (PPN) and 1-diethoxyphosphoryl-1-methyl-N-[(1-oxido-pyridin-1-ium-4-yl) methylidene] ethylamine N-oxide (4-PyOPN) compared with PBN on (1) the evolution of cardiovascular parameters and (2) the postischaemic recovery. Anaesthetized rats were injected with 120 micro mol/kg of the nitrones or 14 micro mol/kg of amiodarone, used as a reference antidysrhythmic drug. Ischaemia was induced in vivo through ligation of the left anterior descending coronary artery for 5 min followed by 15 min of reperfusion after release. Cardiovascular parameters and occurrence of ventricular premature beats (VPB), ventricular tachycardia (VT) and fibrillation (VF) were recorded throughout the experiment. Under nonischaemic conditions, none of the three spin traps was shown to modify cardiovascular parameters during the 25-min measurement period. Solvent-treated (NaCl 0.9%) animals challenged with ischaemia-reperfusion exhibited 39 +/- 10 VPB, 156 +/- 39 s of VT and 60% mortality caused by sustained VF. Nitrones improved slightly postischaemic recovery, reducing the occurrence of VF and mortality to 33% whereas amiodarone injection totally suppressed rhythm disturbances and mortality. Our study has shown only limited antidysrhythmic cardioprotective effects of PBN-derived beta-phosphorylated nitrones during reperfusion after a regional myocardial ischaemia but also minor antioxidant properties of these spin trapping agents.

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Foetal supraventricular tachycardia with hydrops fetalis: a role for direct intraperitoneal amiodarone

et al. 2014

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Disposition of amiodarone in rats after single and multiple intra-peritoneal doses

Cited by 4 publications

References 14 publications

Effect of Amiodarone on Phospholipid Content and Composition in Heart, Lung, Kidney and Skeletal Muscle: Relationship to Alteration of Thyroid Function

Effect of Amiodarone on Phospholipid Content and Composition in Heart, Lung, Kidney and Skeletal Muscle: Relationship to Alteration of Thyroid Function

Effect of two new PBN‐derived phosphorylated nitrones against postischaemic ventricular dysrhythmias

Foetal supraventricular tachycardia with hydrops fetalis: a role for direct intraperitoneal amiodarone

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