Concomitant Intake of Coca-Cola to Manage the Drug-Drug Interaction Between Velpatasvir and Omeprazole Studied in Healthy Volunteers

Minou van Seyen, Angela Colbers, Evertine J Abbink, Joost P H Drenth, David M Burger, Minou van Seyen, Angela Colbers, Evertine J Abbink, Joost P H Drenth, David M Burger

Abstract

We aimed to evaluate the effect of the acid beverage Coca-Cola on the pharmacokinetics of velpatasvir (VEL) when given with omeprazole. This was an open-label, randomized, crossover trial in 11 healthy adults. A single dose of sofosbuvir/velpatasvir (SOF/VEL) 400/100 mg was administered alone (reference) or with omeprazole 40 mg once daily with water (intervention I); in the intervention II arm, omeprazole 40 mg was combined with 250 mL of Coca-Cola. Geometric mean ratios (GMRs) were calculated for VEL area under the concentration-time curve from zero to infinity (AUC0-inf ) and maximum plasma concentration (Cmax ). VEL exposure was reduced by 26.7% when SOF/VEL was coadministered with omeprazole vs. reference: GMRs (90% confidence interval (CI)) were 73.3% (55.6-96.8) and 69.1% (52.3-91.2) for AUC0-inf and Cmax , respectively. Intake of SOF/VEL with Coca-Cola compensated for the interaction with omeprazole and resulted in a higher VEL exposure. GMRs (90% CI) were 161.6% (122.4-213.3) for AUC0-inf and 143.9% (109.0-190.0) for Cmax . Therefore, Coca-Cola can be used to overcome the drug-drug interaction between VEL and omeprazole.

Trial registration: ClinicalTrials.gov NCT03513393.

Conflict of interest statement

D.B. and J.D. have received research grants from Gilead, the manufacturer of velpatasvir; J.D. has been part of an advisory board for Gilead. All other authors declared no competing interests for this work.

© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1
Figure 1
Mean plasma concentration‐time curves for velpatasvir (VEL) after administration of a single dose sofosbuvir/VEL in fasted state for each treatment arm. OME, omeprazole.
Figure 2
Figure 2
Velpatasvir area under the concentration‐time curve from zero to infinity (AUC 0−inf) after administration of a single dose of sofosbuvir/velpatasvir in the fasted state for each treatment arm. Each line represents an individual subject. OME, omeprazole; VEL, velpatasvir.

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