Effect of food on the antiviral activity of didanosine enteric‐coated capsules: a pilot comparative study^*

Abstract

ObjectivesTo determine the effect of food on the antiviral activity of enteric-coated (EC) capsules of didanosine (ddI). MethodsWe conducted a pilot, randomized, open-label study of 28-day ddI-EC capsules monotherapyadministered in a fasted state (group 1, n 5 11) or with food (group 2, n 5 10) to treatment-naïve chronically HIV-1-infected individuals. To assess the antiviral efficacy, HIV-1 RNA was determined at baseline, day 3, day 7 and weekly thereafter. The area under the HIV-1 RNA curve minus baseline weighted by time (AUCMB/day) was calculated. ResultsMean baseline HIV-1 RNA was 4.2 log 10 copies/mL in group 1 and 3.8 log 10 copies/mL in group 2. After 28 days, the mean HIV-1 RNA reduction was 0.99 log 10 copies/mL [95% confidence interval (CI) 0.45-1.53] for group 1 and 0.89 log 10 copies/mL (95% CI 0.38-1.40) for group 2. AUCMB/day values were 0.775 log 10 copies/mL (95% CI 0.33-1.22) and 0.774 log 10 copies/mL (95% CI 0.48-1.07), respectively, showing no difference in the rate of decrease of HIV-1 RNA (P 5 0.995). Mean ddI plasma levels at day 28 were 0.0234 mg/L for group 1 and 0.0227 mg/L for group 2 (P 5 0.96). ConclusionsIn this pilot study, the administration of food did not have any significant effect on the antiviral activity of ddI-EC capsules.

Interactions of Antiretroviral Drugs with Food, Beverages, Dietary Supplements, and Alcohol: A Systematic Review and Meta-analyses

“…The formulation of an antiretroviral drug could be another factor determining the onset and magnitude of interaction with food. For didanosine, in studies of enteric-coated capsules instead of tablets, less distinct postprandial changes in pharmacokinetic parameters occurred [ 53 , 61 ]. Moreover, for enteric-coated capsules taken with or without food, similar antiretroviral activity was reported after 28 days [ 61 ].…”

“…For didanosine, in studies of enteric-coated capsules instead of tablets, less distinct postprandial changes in pharmacokinetic parameters occurred [ 53 , 61 ]. Moreover, for enteric-coated capsules taken with or without food, similar antiretroviral activity was reported after 28 days [ 61 ]. The enteric-coated formulation may be preferable over tablets, as it protects didanosine from hydrolysis in the presence of gastric acid and improves its AUC as well [ 53 ].…”

Clinical perspective on antiretroviral drug–drug interactions with the non-nucleoside reverse transcriptase inhibitor etravirine

“…Enteric-coated didanosine is recommended to be taken on an empty stomach as food moderately decreases its exposure (by 20-25%) [18]; however, no decrease in efficacy was observed in studies of entericcoated didanosine when administered with food [19][20][21]. Coadministration of didanosine and etravirine simultaneously with food has not been evaluated.…”

Safety and Efficacy of Didanosine Enteric-Coated Capsule in Patients with HIV-1 Infection

“…The mean ddI level in the fasting group was 0.0234 mg/l whereas it was 0.0227 in the other group (p = 0.96) at day 28. 5 In an open-label study (GESIDA-3903) comparing EFV with either ddI-EC/3TC OD or zidovudine (AZT)/3TC twice daily, both regimens were administered with food. The study included 369 ART-naïve participants and 70% of those randomized to the ddI-EC arm and 63% of the patients on the AZT arm had HIV-1 RNA levels  50 copies/ml at week 48 respectively, in an intention-to-treat (ITT) analysis.…”

“…The mean ddI level in the fasting group was 0.0234 mg/l whereas it was 0.0227 in the other group (p = 0.96) at day 28. 5…”