Serum belumosudil concentrations in a patient receiving a combination of 3 gastric acid-suppressing agents: A case report.

Belumosudil is an orally administered selective ROCK2 inhibitor used in the treatment of chronic graft-vs-host disease. Given that pharmacological activity has been reported to be concentration dependent, factors affecting absorption must be carefully considered. As a weakly basic drug, belumosudil shows pH-dependent solubility, with elevated gastrointestinal pH significantly reducing its solubility and absorption. While proton pump inhibitors are known to markedly decrease the absorption of belumosudil, data on interactions with other acid-suppressing agents remain limited. This report describes a patient with graft-vs-host disease and bronchiolitis obliterans who was treated with belumosudil alongside various acid-suppressing agents to manage gastrointestinal symptoms and prevent bleeding. The patient sequentially received oral famotidine, intravenous omeprazole, and vonoprazan. Belumosudil was administered once daily after breakfast, while famotidine and vonoprazan were administered after lunch and omeprazole was administered 2 and 9 hours after belumosudil. Trough serum concentrations of belumosudil were 284 ng/mL (without acid-suppressive therapy), 223 ng/mL (with famotidine), and 205 ng/mL (with vonoprazan), while peak concentrations were 1,917 ng/mL (with omeprazole) and 3,162 ng/mL (with vonoprazan). Although coadministration with a proton pump inhibitor has been reported to markedly reduce belumosudil exposure, coadministration with the more potent acid suppressant vonoprazan resulted in only a modest decrease in this case. These findings suggest that the extent of interaction between acid-suppressive agents and belumosudil may vary depending on individual factors, such as drug timing and interpatient variability in acid suppression. Further research is needed to develop comprehensive management strategies for patients requiring concurrent belumosudil and acid-suppressing therapy.