Amiodarone is a pharmacologically safe drug for porphyrias.
Amiodarone (AD) is an effective antidysrythmic drug, however, there can be serious side effects, such as hepatic and neurological alterations, as well as skin photosensitization, as seen in porphyrias. Clinical signs in porphyrias might be triggered by the so-called porphyrinogenic drugs. Without sound basis, Amiodarone has been classified as an unsafe drug for porphyric patients. The aim of this work has been to study the effect of AD, both in vivo and in vitro, on heme metabolism. In the in vivo assays, the activities of 5-aminolevulinate synthetase (ALA-S), ALA dehydratase (ALA-D), porphobilinogenase (PBGase) and PBG-deaminase (PBG-D) in blood, liver, and kidney; hepatic and fecal porphyrins, urinary ALA, PBG and porphyrins in male mice strain CF1 treated with AD (100 mg i.p. daily) for 1 week and 1 month, were measured. No significanat differences were found for any of these parameters in the AD treated animals as compared to controls. In the in vitro experiments human blood, and mice blood, liver, and kidney, were used to measure the activities of ALA-S, ALA-D, PBGase, PBG-D and uroporphyrinogen decarboxylase, in the presence of varying concentrations of AD (0.0172-4.304 mM). AD did not modify any of the enzyme activities. All of the above biochemical parameters were studied in 17 cardiac patients under AD treatment for 3 to 20 years. Neither the activities of the heme enzymes, nor the levels of precursors and porphyrins in urine and plasma were altered. These findings clearly demonstrate that AD is a pharmacologically safe drug and can be used for the treatment of associated pathologies in porphyrias.
Méndez
M
M
Centro de Investigaciones sobre Porfirinas y Porfirias-CIPYP (CONICET, Department Biochemistry, School of Sciences, University of Buenos Aires), Argentine.
Parera
V
V
Enríquez de Salamanca
R
R
Batlle
A
A
D000624:5-Aminolevulinate Synthetase / Q000097:blood / Q000378:metabolism; D000638:Amiodarone / Q000627:therapeutic use*; D000642:Ammonia-Lyases / Q000097:blood; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D005243:Feces / Q000737:chemistry; D006331:Heart Diseases / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D011164:Porphyrias / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism* / Q000652:urine
D000889:Anti-Arrhythmia Agents; D011166:Porphyrins; D000624:5-Aminolevulinate Synthetase; D000642:Ammonia-Lyases; C100132:porphobilinogenase; D000638:Amiodarone