Effect of antiepileptic drugs on the urinary excretion of porphyrins in non-porphyric subjects.

Abstract

The action of some anticonvulsant drugs as the causal agents of attacks of acute porphyria has been widely documented in the literature. However, little attention has been paid to the effect of these drugs on the urinary excretion of porphyrins in non-porphyric subjects. In a sample of 82 epileptic patients treated with phenobarbital (n = 54), phenytoin (n = 64), carbamazepine (n = 33), and valproate (n = 8), the daily doses were expressed according to a drug score that would reflect the capacity of these drugs as enzymatic inducers when administered in polytherapy. A significantly increased urinary excretion of D-glucaric acid (DGA) and porphyrins was found in this group of patients (P<0.001), with coproporphyrin being the major fraction in all cases (>60%). Urinary DGA had a highly significant correlation with the drug score (r = 0.783, P<0.001); however, no significant correlations were found between the urinary porphyrins and DGA (r = 0.005) or the drug score (r = 0.053). Neither was any significant relationship found between the urinary porphyrins and the serum activity of 5'-nucleotidase (r = 0.066) or the presence of a cholestasis objectivized through the presence of the isoform of gamma-glutamyltransferase with beta-globulins electrophoretic mobility. However, in a group of 10 patients a significant correlation was found between the urinary excretion of porphyrins and beta-N-acetylhexosaminidase (r = 0.790, P<0.01). Therefore, it does not appear that the liver enzyme induction, or even a subclinical cholestasis, produced by the antiepileptic drugs administered to these patients may serve to explain the increase in the urinary excretion of porphyrins. A possible renal origin is proposed for the increase of urinary porphyrins in these cases.

• Authors: Maria J Tutor-Crespo, Jesús Hermida, J Carlos Tutor
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 99 Issue 4 Pg. 323-8 (Dec 2005) ISSN: 1347-8613 [Print] Japan
• PMID: 16314692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Enzymes
• Porphyrins
• Pyridoxal Phosphate
• Transaminases
• Glucaric Acid

Topics

• Adult
• Anticonvulsants (adverse effects, therapeutic use)
• Cholestasis (urine)
• Enzyme Induction (drug effects)
• Enzymes (urine)
• Epilepsy (drug therapy, urine)
• Female
• Glucaric Acid (urine)
• Humans
• Male
• Middle Aged
• Porphyrias (urine)
• Porphyrins (urine)
• Pyridoxal Phosphate (pharmacology)
• Transaminases (blood)