Effects of Tenapanor on Cytochrome P450‐Mediated Drug‐Drug Interactions

@article{Johansson2017EffectsOT,
  title={Effects of Tenapanor on Cytochrome P450‐Mediated Drug‐Drug Interactions},
  author={Susanne Johansson and David P Rosenbaum and Marie Ahlqvist and Helen E Rollison and Mikael Knutsson and Bergur V. Stef{\'a}nsson and Marie Elebring},
  journal={Clinical Pharmacology in Drug Development},
  year={2017},
  volume={6},
  pages={466 - 475}
}
Tenapanor (RDX5791, AZD1722) is an inhibitor of sodium/hydrogen exchanger isoform 3 in development for the treatment of constipation‐predominant irritable bowel syndrome and the treatment of hyperphosphatemia in patients with chronic kidney disease on dialysis. We aimed to investigate whether tenapanor inhibits or induces cytochrome P450s (CYPs). In vitro experiments assessing the potential of tenapanor to affect various CYPs indicated that it could inhibit CYP3A4/5 (IC50 0.4‐0.7 μM). An open… Expand

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References

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TLDR
Tenapanor treatment reduced absorption of intestinal sodium and phosphate from the gut in Japanese adults and had minimal systemic exposure and was well tolerated. Expand
Dose-Dependent Interaction between Gemfibrozil and Repaglinide in Humans: Strong Inhibition of CYP2C8 with Subtherapeutic Gemfibrozil Doses
TLDR
The gemfibrozil-repaglinide interaction could be mainly explained by gemfirzil 1-O-β-glucuronide concentration-dependent, mechanism-based inhibition of CYP2C8, with a minor contribution by competitive inhibition of organic anion-transporting polypeptide 1B1 at the highest gemfiberzil dose. Expand
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TLDR
Tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis, and diarrhea was the most common adverse event. Expand
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TLDR
The current state of knowledge of CYP enzyme expression in human small intestine, the role of the gut wall in CYP-mediated metabolism, and how this metabolism limits the bioavailability of orally administered drugs are reviewed. Expand
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TLDR
Tenapanor treatment increased stool sodium and weight over placebo in patients undergoing hemodialysis, but over 4 weeks of treatment, there was no difference in interdialytic weight gain between patients treated with tenapanor and those receiving placebo. Expand
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TLDR
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