Abstract
BACKGROUND: Sirolimus is primarily metabolized by CYP3A4 and transported by P-gp. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted sirolimus concentrations. CASE SUMMARY: In this case report, we investigate a pharmacokinetic drug-drug interaction between regorafenib and sirolimus, mediated by CYP3A4 and P-gp, in a 56-year-old Chinese male with recurrent hepatocellular carcinoma post-liver transplantation. In this case, the patient's baseline sirolimus trough blood concentration was 5.0 ng/mL prior to initiating a new cycle of regorafenib (80 mg once daily). Following a 7-day administration period of regorafenib, a notable elevation in sirolimus trough blood concentration to 12.3 ng/mL was observed. Upon cessation of regorafenib therapy for one week, the sirolimus trough blood concentration reverted back to 5.2 ng/mL. Nevertheless, upon resumption of regorafenib (160 mg once daily) treatment for an additional 10 days, the sirolimus trough blood concentration experienced a recurrence of increase, reaching 11.0 ng/mL. Following the confirmation of tumor progression, the discontinuation of regorafenib was deemed necessary. Consequently, a subsequent medical evaluation of the patient's sirolimus trough blood concentration, undertaken precisely one month after cessation of regorafenib therapy, revealed a concentration level of 2.8 ng/mL. Based on the Drug Interaction Probability Scale, this interaction was deemed probable. CONCLUSION: Regorafenib exerts a regulatory influence on the blood concentrations of sirolimus by inhibiting the activity of CYP3A4 and P-gp, potentially altering its pharmacokinetic profile. Given the potential for both excessive and inadequate immunosuppression to adversely affect patients with recurrent hepatocellular carcinoma post-liver transplantation, clinicians must maintain a heightened awareness of this drug-drug interaction.