释义 n. 奥美拉唑
例句 To study the relation of CYP2C19 genotype to omeprazole metabolism in Chinese healthy subjects.
作者： van Seyen M
期刊：Clin Pharmacol Ther
The fixed-dose combination of the NS5B polymerase inhibitor sofosbuvir (SOF) and the NS5A inhibitor velpatasvir (VEL) is a pan-genotypic, once-daily tablet for the treatment of chronic hepatitis C virus (HCV) infection. VEL is a lipophilic weak base (Log D 6.31 (pH 8); acid dissociation constants [pKa] 3.2 and 4.6(1)) with pH dependent solubility ranging from soluble at pH 1.2 (> 36 mg/mL) to practically insoluble above pH4.5 (< 0.1 mg/mL) (2, 3). As a result, pH-dependent dissolution of the drug is a rate-limiting step for absorption. In general, proton pump inhibitors (PPIs) elevate the stomach pH and achieve a gastric pH>4 by reducing gastric secretion (4). This increase in gastric pH impairs VEL absorption. It has been shown that in subjects treated with omeprazole, the absorption of VEL is reduced by 26-56%, depending on the dose of omeprazole, concomitant food intake, and timing/sequence of VEL versus omeprazole intake (5, 6). This is the reason why concomitant use of SOF/VEL with PPIs (such as omeprazole) is not recommended. The package insert recommends to administer SOF/VEL with food and taken 4 hours before PPI at maximum doses comparable to omeprazole 20 mg, if PPI use is necessary (6).