Tolonen, H, Ranta, S, Hämäläinen, E, Kauppinen, R, Hukkanen, J. Effects of rifampicin on porphyrin metabolism in healthy volunteers. Basic Clin Pharmacol Toxicol. 2023; 132( 3): 281- 291. doi:10.1111/bcpt.13826
Effects of rifampicin on porphyrin metabolism in healthy volunteers
|Author:||Tolonen, Hanna1,2,3; Ranta, Sirpa4; Hämäläinen, Esa5;|
1Research Unit of Internal Medicine, University of Oulu, Oulu, Finland
2Biocenter Oulu, University of Oulu, Oulu, Finland
3Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
4Clinical Chemistry, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
5School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2023031632108
John Wiley & Sons,
|Publish Date:|| 2023-12-19
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.
Basic & clinical pharmacology & toxicology
|Pages:||281 - 291|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by the Diabetes Research Foundation, the Finnish Foundation for Cardiovascular Research, the Northern Finland Health Care Support Foundation, Finnish Government Grants for Health Research, and the Finnish Medical Foundation.
© 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Tolonen, H, Ranta, S, Hämäläinen, E, Kauppinen, R, Hukkanen, J. Effects of rifampicin on porphyrin metabolism in healthy volunteers. Basic Clin Pharmacol Toxicol. 2023; 132( 3): 281- 291, which has been published in final form at https://doi.org/10.1111/bcpt.13826. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.