Effects of rifampicin on porphyrin metabolism in healthy volunteers
Pregnane X receptor (PXR) is known to stimulate haem synthesis, but detailed knowledge on the effects of PXR activation on porphyrin metabolism in humans is lacking. We utilized a randomized, crossover, open (blinded laboratory) and placebo‐controlled trial with 600‐mg rifampicin or placebo dosed fo...
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Published in | Basic & clinical pharmacology & toxicology Vol. 132; no. 3; pp. 281 - 291 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Wiley Subscription Services, Inc
01.03.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Pregnane X receptor (PXR) is known to stimulate haem synthesis, but detailed knowledge on the effects of PXR activation on porphyrin metabolism in humans is lacking. We utilized a randomized, crossover, open (blinded laboratory) and placebo‐controlled trial with 600‐mg rifampicin or placebo dosed for a week to investigate the effects of PXR activation on erythrocyte, plasma, faecal and urine porphyrins. Sixteen healthy volunteers participated on the trial, but the number of volunteers for blood and urine porphyrin analyses was 15 while the number of samples for faecal analyses was 14. Rifampicin increased urine pentaporphyrin concentration 3.7‐fold (mean 1.80 ± 0.6 vs. 6.73 ± 4.4 nmol/L, p = 0.003) in comparison with placebo. Urine coproporphyrin I increased 23% (p = 0.036). Faecal protoporphyrin IX decreased (mean 31.6 ± 23.5 vs. 19.2 ± 27.8 nmol/g, p = 0.023). The number of blood erythrocytes was slightly elevated, and plasma bilirubin, catabolic metabolite of haem, was decreased. In conclusion, rifampicin dosing elevated the excretion of certain urinary porphyrin metabolites and decreased faecal protoporphyrin IX excretion. As urine pentaporphyrin and coproporphyrin I are not precursors in haem biosynthesis, increased excretion may serve as a hepatoprotective shunt when haem synthesis or porphyrin levels are increased. |
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Bibliography: | Funding information Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Northern Finland Health Care Support Foundation; Finnish Government Grants for Health Research; Finnish Medical Foundation ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
ISSN: | 1742-7835 1742-7843 |
DOI: | 10.1111/bcpt.13826 |