Drug intelligence / Profile preview

ritonavir + atazanavir + rabeprazole

Development stage
Unknown
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Oral
01

Overview

This is a non-standard, three-drug combination consisting of ritonavir, atazanavir, and rabeprazole. Ritonavir and atazanavir are both antiretroviral protease inhibitors used in the treatment of HIV-1 infection. Ritonavir is primarily used as a pharmacokinetic booster to increase plasma concentrations of other protease inhibitors like atazanavir by inhibiting cytochrome P450 3A4 (CYP3A4). Atazanavir inhibits the HIV-1 protease enzyme, preventing viral replication. Rabeprazole is a proton pump inhibitor (PPI) that reduces gastric acid secretion by irreversibly inhibiting the H+/K+ ATPase in gastric parietal cells; it is typically used for gastroesophageal reflux disease or peptic ulcer disease. The co-administration of rabeprazole with ritonavir-boosted atazanavir is not recommended due to significant drug-drug interactions. Rabeprazole-induced hypochlorhydria markedly decreases the absorption and systemic exposure of atazanavir (by up to 70%), which can compromise antiretroviral efficacy[3][6]. While some clinical data suggest this may not always lead to virologic failure in all patients, current guidelines advise against this combination unless absolutely necessary and under close monitoring[2][6][7].

02

Targets

CYP3A4 (Cytochrome P450 3A4)ATP4A (Potassium–transporting ATPase alpha chain 1)PR (Progesterone receptor)

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