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Effects of Rifampicin on the Pharmacokinetics and Safety of Carotegrast Methyl in Healthy Subjects: A Randomized 2 x 2 Crossover Study
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  • Hiromitsu Imai,
  • Ichiro Oikawa,
  • Tetsuya Koyama,
  • Shunji Matsuki
Hiromitsu Imai
Oita University Faculty of Medicine
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Ichiro Oikawa
Oita University Faculty Of Medicine Graduate School of Medicine
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Tetsuya Koyama
EA Pharma Co Ltd

Corresponding Author:[email protected]

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Shunji Matsuki
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Aims: To evaluate the effect of the combination of carotegrast methyl with rifampicin, a potent inhibitor of organic anion transporter polypeptide, on the pharmacokinetics (PK), safety and tolerability. Methods: In this 2 x 2 crossover study in 20 healthy Japanese adults, 10 subjects received carotegrast methyl 960 mg and rifampicin 600 mg on day 1, and received carotegrast methyl 960 mg on day 8. The subjects in the other sequence received the same treatments but in the opposite order. When the 90% confidence interval (CI) of the geometric mean ratio of the AUC0-t and Cmax for carotegrast, the main active metabolite of carotegrast methyl, with/without rifampicin fell within the range of 0.80 – 1.25, it was deemed that no PK interaction occurred. Adverse events (AEs) were monitored. Results: The Cmax and AUC0-t for carotegrast with/without rifampicin was 11724.5 ± 6097.6 vs 2620.1 ± 1843.0 ng mL-1, and 55046.0 ± 23427.8 vs 9849.9 ± 4580.6 ng h mL-1, respectively. The ratios (90% CI) of the Cmax and AUC0-t with/without rifampicin were 4.78 (3.64 – 6.29) and 5.59 (4.60 – 6.79), respectively, indicating carotegrast has a PK interaction with rifampicin. The combination with rifampicin also increased the exposure of carotegrast and its metabolites. The incidence of any AEs with/without rifampicin was five (25.0%) and one (5.0%), respectively. Conclusion: Coadministration of carotegrast methyl with rifampicin significantly increased exposure of carotegrast compared with carotegrast methyl administration alone. However, no increase in the incidence of adverse drug reactions due to coadministration with rifampicin was observed.
28 Sep 2023Submitted to British Journal of Clinical Pharmacology
28 Sep 2023Assigned to Editor
28 Sep 2023Submission Checks Completed
28 Sep 2023Review(s) Completed, Editorial Evaluation Pending
30 Sep 2023Reviewer(s) Assigned
23 Oct 2023Editorial Decision: Revise Major