Vonoprazan is a potassium competitive acid blocker (PCAB) that inhibits the H+, K+- atpase system in a potassium competitive manner. Through this mechanism, vornopiperazine inhibits the basic gastric acid secretion on the secretion surface of gastric parietal cells and stimulates gastric acid secretion.
Although both types of drugs can inhibit H+and K+- atpases, the mechanism of action of pcab is different from proton pump inhibitors (PPIs). PPIs form covalent disulfide bonds with cysteine residues on H+, K+- atpase, leading to enzyme inactivation, while ppab interferes with the binding of K+to H+, K+- atpase.
Vonoprazan has a time independent pharmacokinetics and reaches a steady-state concentration after 3-4 days. The AUC0-12h, Cmax, and Tmax of single dose patients were 154.8 ng/mL, 25.2 ng/mL, and 2.5 h, respectively. The AUC0-12h, Cmax, and Tmax of patients treated twice a day were 272.5 ng/mL, 37.8 ng/mL, and 3.0 h, respectively. Patients who received daily doses of 10 to 40 mg showed a dose-proportional increase in AUC and Cmax. After taking 20 milligrams of Vonoprazan in healthy subjects, a high fat diet resulted in a 5% and 15% increase in Cmax and AUC, respectively; However, these changes are considered clinically insignificant.
Vonoprazan is metabolized by several cytochrome P450 (CYP) subtypes, mainly CYP3A4, followed by CYP3A5, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. Sulfonyltransferase and glucuronyltransferase are also involved in the metabolism of vornopiperazine, and all metabolites have no pharmacological activity. CYP3A4 converts vornopiperazine into metabolites M-I and M-II, and then converts them into glucuronic acid coupling products M-I - g and M-II - g, respectively. Unlike proton pump inhibitors, the presence of CYP2C19 polymorphism did not significantly affect the pharmacokinetics of vornoprazine.
There have been no reports of excessive use of Vonoprazan. In clinical studies, no serious adverse reactions were observed with a single dose of 120 mg of Vonoprazan. Vonoprazan cannot be cleared from the bloodstream through hemodialysis. In the case of overdose, FDA labels Voquezna Triple Pack and Voquezna Double Pack suggest symptomatic and supportive treatment.
The animal study evaluating the mutagenicity of vonoprazan (Ames test) reported negative results. Oral administration of Vonoprazan 300 mg/kg/day (maximum recommended dose in humans 133 mg/kg/day) to rats did not observe any effects on their fertility and reproductive performance. Oral administration of 6, 20, 60, and 200 mg/kg/day of Vonoprazan (0.4, 4, 19, and 93 times the maximum recommended dose in humans) resulted in neuroendocrine cell proliferation, gastric disease, and benign and/or malignant neuroendocrine cell tumors (carcinoids) in mice.
Article source: https://article-realm.com/article/Health-Fitness/45113-Vonoprazan-is-metabolized-by-several-cytochrome-P450-CYP-subtypes.html
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