Abstract
Patients with any of the acute porphyrias may suffer from acute attacks. If these patients are treated with certain drugs, such as barbiturates, the likelihood of developing an attack is increased. Patients treated with antidepressants or benzodiazepine-type anxiolytics also could be placed at increased risk of developing porphyric attacks because little is known about the potential for some of these drugs to induce attacks. Primary cultures of chick embryo liver cells were used to study the effects of selected antidepressants and anxiolytics on porphyrin accumulation. Cells were treated with desferrioxamine (to partially block heme synthesis, simulating conditions encountered in porphyric patients) and increasing concentrations (3.16–1000 μM) of the evaluated drugs. Twenty hours later, porphyrin accumulation was measured. The drugs included four antidepressants and five benzodiazepine-type anxiolytics. The antidepressants bupropion and nefazodone significantly increased porphyrin accumulation when given with desferrioxamine, whereas neither fluoxetine nor paroxetine increased porphyrin accumulation. The benzodiazepine-type anxiolytic agents oxazepam, lorazepam, diazepam, triazolam, and midazolam all significantly increased porphyrin accumulation when given with desferrioxamine. Dose-response studies showed that diazepam, midazolam, and triazolam produced significant increases even at the lowest concentration tested (3.16 μM), whereas lorazepam and oxazepam required higher concentrations (≥10 μM). These studies suggest that patients with acute porphyrias may be at greater risk for developing porphyric attacks when treated with bupropion or nefazodone compared with fluoxetine or paroxetine, and that the evaluated benzodiazepine derivatives should be administered with caution. Among the latter, low doses of lorazepam and oxazepam may be safer than those of diazepam, midazolam, and triazolam.
Footnotes
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Send reprint requests to: Herbert L. Bonkovsky, M.D., Director, Digestive Disease and Nutrition, Department of Medicine, UMass Memorial Health Care, Rm. S6-737, 55 Lake Ave., North, Worcester, MA 01655-0317. E-mail: richard.lambrecht{at}umassmed.edu
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↵1 This work was supported by a grant from the U.S. Public Health Service (National Institutes of Health) (DK38825 to H.L.B.) and the Undergraduate Summer Research Stipend from the University of Massachusetts (to A.W.). The opinions expressed in this paper are those of the authors; they do not necessarily reflect the official views of the U.S. Public Health Service or the National Institutes of Health.
- Abbreviations:
- ALA
- 5-aminolevulinate
- CELC
- chick embryo liver cell
- DES
- desferrioxamine
- DMSO
- dimethyl sulfoxide
- PB
- phenobarbital
- Received April 13, 1999.
- Accepted August 19, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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