NCT07196449

Drug-Drug Interaction of Rifampicin and Cyclosporine on Methotrexate Pharmacokinetics in Healthy Subjects

A Drug-drug Interaction Study to Evaluate the Effect of Rifampicin and Cyclosporine on the Pharmacokinetics of Methotrexate in Healthy Subjects

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Seoul National University Bundang Hospital · Academic / Other
• Sex: Male
• Age: 19 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This study will evaluate how methotrexate is processed in the body when given with low doses of rifampicin or cyclosporine. These drugs may affect how methotrexate is absorbed and cleared, which could change its safety and effectiveness. Healthy volunteers will receive methotrexate with either rifampicin or cyclosporine, and blood samples will be collected to measure drug levels. The findings may help identify possible drug interactions and improve the safe use of methotrexate.

Detailed description

Unexpected or unrecognized drug-drug interactions can reduce efficacy, cause toxicity, or even lead to fatal outcomes. Inhibition or induction of drug transporters involved in hepatic or renal uptake/efflux may alter drug exposure, affecting safety and efficacy. The FDA requires clinically significant interactions to be assessed prior to approval. OATPs (primarily hepatic uptake) and BCRP (hepatic and renal efflux) share many substrates, but their combined inhibition has not been well studied in humans. Methotrexate, a substrate of both OATP and BCRP, is widely used at varying doses for cancer, psoriasis, and rheumatoid arthritis, often in combination with other drugs such as NSAIDs, which may result in interactions requiring close monitoring. Rifampicin, an antibiotic, inhibits OATP1B1/1B3 in a dose-dependent manner, while cyclosporine, an immunosuppressant, inhibits OATP and BCRP. In our previous study (IRB No. B-2110-715-001), the investigators quantitatively demonstrated that rifampicin reduces 7-OH-methotrexate formation via OATP inhibition. However, dose-dependent inhibition by rifampicin and the impact of cyclosporine on methotrexate pharmacokinetics remain unclear. This study aims to evaluate the pharmacokinetics of methotrexate following co-administration with low-dose rifampicin (150 or 300 mg) and cyclosporine in healthy volunteers. The investigators will also explore the role of methotrexate metabolites as potential biomarkers to assess OATP-mediated interactions.

Conditions

• Drug Drug Interaction (DDI)

Interventions

Type	Name	Description
DRUG	Methotrexate	Methotrexate Tab. 2.5 mg (Korea United Pharm)
DRUG	Rifampicin	Rifampin Cap. 150 mg (Yuhan Corporation)
DRUG	Cyclosporine	Cypol-N Cap. 100 mg (Chong Kun Dang)

Timeline

• Start date: 2025-05-14
• Primary completion: 2025-06-09
• Completion: 2026-04-14
• First posted: 2025-09-29
• Last updated: 2025-09-29

Locations

1 site across 1 country: South Korea