Effects of rifampicin on porphyrin metabolism in healthy volunteers

• Published in: Basic & clinical pharmacology & toxicology Vol. 132; no. 3; pp. 281 - 291
• Main Authors: Tolonen, Hanna, Ranta, Sirpa, Hämäläinen, Esa, Kauppinen, Raili, Hukkanen, Janne
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2023
• Subjects: Bilirubin; Biosynthesis; Blood; coproporphyrin I; Erythrocytes; Excretion; Haem; Healthy Volunteers; Heme - metabolism; Humans; Metabolism; Metabolites; pentaporphyrin; Placebos; Porphyrins; Porphyrins - metabolism; Porphyrins - urine; pregnane X receptor; Pregnane X Receptor - drug effects; Pregnane X Receptor - metabolism; Protoporphyrin; Protoporphyrin IX; rifampicin; Rifampin; Rifampin - pharmacology; Urine; coproporphyrin I; rifampicin; pregnane X receptor; protoporphyrin IX; pentaporphyrin
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13826

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.