rifampicin

P1, N=20, Recruiting, Brigham and Women's Hospital | Trial completion date: Mar 2025 --> Dec 2026 | Trial primary completion date: Mar 2025 --> Dec 2026

P1, N=63, Completed, Incyte Corporation | Recruiting --> Completed

P1, N=42, Not yet recruiting, Celgene

P1, N=51, Recruiting, Incyte Corporation | Completed --> Recruiting | N=15 --> 51 | Trial completion date: May 2025 --> Mar 2026 | Trial primary completion date: May 2025 --> Feb 2026

Antibiotics such as doxycycline, rifampicin, and azithromycin demonstrate anticancer properties by inhibiting angiogenesis, inducing apoptosis, and regulating key pathways including the interleukin (IL)-6 signaling pathway and autophagy-related pathways. By elucidating the pivotal role of biofilms in persistent infections and highlighting untapped therapeutic opportunities in antibiotic repurposing, this review underscores a transformative approach to cancer treatment. This article explores the potential of repurposing antibiotic drugs for cancer treatment and highlights the prospects of drug repurposing strategies.

Pharmacokinetic (PK) studies were performed in Sprague-Dawley (SD) rats following oral and intravenous dosing, including coadministration with CYP3A4 inhibitors (voriconazole, itraconazole) and inducers (rifampicin, carbamazepine). Significant interspecies differences between HLM and RLM emphasize the need for caution when translating preclinical findings. Coadministration with CYP3A4 modulators markedly altered systemic exposure, while effective brain penetration supports its therapeutic role in central nervous system (CNS) metastases.

P2, N=60, Not yet recruiting, Beijing Chest Hospital, Capital Medical University; WestVac Biopharma Co., Ltd.

The PBPK model captured the clinically observed interactions for itraconazole, rifampin, and midazolam, with predicted pirtobrutinib and midazolam AUC ratios within 0.91- to 1.16-fold of observed. Furthermore, the predicted pirtobrutinib AUC ratios were within 0.51-0.86 with moderate and weak CYP3A4 inducers. The predicted effects of CYP3A4 modulators on pirtobrutinib pharmacokinetics, together with the known exposure-response relationships for safety and efficacy in patients with hematological malignancies, were used for recommending appropriate dosing regimens during coadministration.

The developed PBPK model was validated against clinical drug-drug interaction studies with a moderate CYP3A inhibitor (fluconazole), a strong CYP3A/P-gp dual inhibitor (itraconazole), and a strong CYP3A/P-gp dual inducer (rifampicin), indicating that the contributions of CYP3A and P-gp in the gut and liver to valemetostat PK were appropriately described in the PBPK model. The validated model was applied to assess the effect of either a CYP3A or a P-gp inhibitor, or a moderate CYP3A inducer on valemetostat PK. The PBPK model incorporating the contribution of CYP3A and P-gp in the gut and liver effectively estimated the effect of CYP3A/P-gp modulators on valemetostat PK and can be used to inform dose recommendations for valemetostat upon coadministration with other treatments.

P=N/A, N=280, Not yet recruiting, Albert Einstein College of Medicine | Trial completion date: Sep 2029 --> Dec 2029 | Trial primary completion date: Mar 2029 --> Jun 2029

A PBPK-informed Phase I clinical DDI study was conducted that evaluated MEZI as an object of CYP3A induction (rifampin) and inhibition (itraconazole) and as a precipitant of transporter-mediated interactions (digoxin and rosuvastatin). This iterative "learn-confirm" approach underscores the utility of PBPK modeling in optimizing clinical trial design, ensuring participant safety, and anticipating DDI risks. The findings support MEZI's clinical development with informed dosing strategies, particularly for coadministration with CYP3A modulators.

P3, N=532, Not yet recruiting, Otsuka Pharmaceutical Development & Commercialization, Inc.