Categories
Change Password!
Reset Password!
Concurrent use of vonoprazan, but not tegoprazan, alters atorvastatin pharmacokinetics in healthy males.
A new study led by Sejung Hwang et al. sheds light on the significant drug interaction between the acid-suppressing agent vonoprazan and the widely used statin, atorvastatin. Unlike its potassium-competitive acid blocker (P-CAB) counterpart tegoprazan, vonoprazan appears to disrupt atorvastatin metabolism—raising safety concerns for patients on combination therapy.
In this open-label, multiple-dose, four-period crossover trial, 28 healthy adult participants received three different 7-day treatment regimens: atorvastatin 40 mg alone, atorvastatin with vonoprazan 20 mg, and atorvastatin with tegoprazan 50 mg. Blood samples were collected up to 24 hours after the final dose to measure pharmacokinetic (PK) parameters of atorvastatin, its active metabolite (2-hydroxyatorvastatin), and its lactone form.
When combined with vonoprazan, systemic exposure to atorvastatin and atorvastatin lactone escalated significantly, while levels of 2-hydroxyatorvastatin dropped—suggesting inhibition of the CYP3A4 enzyme responsible for metabolizing atorvastatin. This change in metabolic profile could potentially heighten the risk of statin-related side effects such as myopathy or liver enzyme elevation.
Moreover, only the vonoprazan group experienced a marked rise in gastrin levels, known as hypergastrinemia—an indicator of hormonal alteration that could carry long-term implications with chronic use. In contrast, tegoprazan did not affect atorvastatin’s PK parameters nor trigger hormonal changes, highlighting a clear pharmacological distinction between the two P-CABs.
These findings emphasize the requisition for clinicians to consider drug-drug interactions beyond acid suppression when prescribing vonoprazan, particularly with medications metabolized by CYP3A4. While vonoprazan’s effectiveness in acid-related disorders is well-established, its interaction profile warrants careful attention—something tegoprazan appears to avoid, at least in the context of atorvastatin.
Frontiers in Pharmacology
Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects
Sejung Hwang et al.
Comments (0)