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 porph yrias might be triggered by the so-called porphyrinogenic drugs. Without so und basis, Amiodarone has been classified as an unsafe drug for porphyric p atients. The aim of this work has been to study the effect of AD, both in v ivo and in vitro, on heme metabolism. In the in vivo assays, the activities of 5-aminolevulinate synthetase (ALA-S), ALA dehydratase (ALA-D), porphobi linogenase (PBGase) and PBG-deaminase (PBG-D) in blood, liver, and kidney; hepatic and fecal porphyrins, urinary ALA, PEG and porphyrins in male mice strain CF1 treated with AD (100 mg i.p. daily) for 1 week and 1 month, were measured. No significant differences were found for any of these parameter s in the AD treated animals as compared to controls. In the in vitro experi ments human bood, and mice blood, liver, and kidney, were used to measure t he activities of ALA-S, ALA-D, PBGase, PBG-D and uroporphyrinogen decarboxy lase, 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 activieis of the heme enzymes, nor the levels of prec ursors and porphyrins in urine and plasma were altered. These findings clea rly demonstrate that AD is a pharmacologically safe drug and can be used fo r the treatment of associated pathologies in porphyrias. (C) 1999 Elsevier Science Inc. All rights reserved.