Effect of Low-Dose Vonoprazan on Hepatic Cytochrome P450 Activity By 13C-Aminopyrine Breath Test in Healthy Subjects.

BACKGROUND Proton pump inhibitors (PPIs) affect hepatic drug metabolism via cytochrome P450 (CYP) enzymes, but the impact of potassium-competitive acid blockers (P-CABs), such as vonoprazan (VPZ), is not fully understood. This study aimed to evaluate whether maintenance-dose VPZ influences hepatic CYP activity using the 13C-aminopyrine breath test (13C-ABT). MATERIAL AND METHODS Twenty healthy subjects aged 18 years or older were recruited. Each participant underwent 13C-ABT under 2 conditions: without treatment (control) and after 8 days of 10 mg VPZ once daily. After oral administration of 100 mg 13C-aminopyrine, breath samples were collected before dosing and every 15-30 minutes for 3 hours. The delta-over-baseline (DOB) ratio, reflecting ¹³CO₂/¹²CO₂, was measured using infrared spectroscopy. RESULTS Nineteen participants (median age 24 years; 10 men, 9 women) completed the study. In the control condition, DOB values increased from 15 minutes after dosing and reached a peak at 49.7±35.8 minutes. The VPZ condition showed no significant differences in the DOB curve compared to the control condition (P=0.316). The area under the DOB curve over 3 hours was comparable between conditions, with a geometric mean ratio of 1.09 (90% confidence interval 0.97-1.23). Peak values and time to peak were also similar between 2 conditions. CONCLUSIONS Administration of 10 mg of VPZ did not significantly affect hepatic CYP activity as assessed by the 13C-ABT, suggesting that VPZ at a maintenance dose has minimal effect on hepatic drug metabolism and drug-drug interactions.