A study conducted by Bristol Myers Squibb, presented at the 4th International Workshop on Clinical Pharmacology of HIV therapy in Cannes last week, confirms that dosing of its anti-HIV drug ddI (didanosine, Videx EC) 250mg once daily with tenofovir 300mg and a light meal results in similar ddI exposure to once daily dosing of Videx 400mg on an empty stomach without tenofovir.
The findings will be submitted to regulatory agencies in Europe and North America with a request for a change in Videx EC labelling. Currently, product labelling warns that Videx EC should not be taken at the same time as food, because regulatory authorities were not convinced by previous studies on the effects of food on ddI absorption. The Videx EC capsule was developed in part to address longstanding concerns over the difficulties created for patients by the need to take ddI on an empty stomach.
The latest study was carried out in 33 healthy volunteers, who were randomised to receive either 400mg or 250mg of ddI in the fasted state at days 1 and 3, before receiving tenofovir 300mg once daily with food from days 4 to 14. In addition, a single dose of ddI (200, 250 or 325mg) was given at days 10, 12 and 14 in a randomised crossover manner (meaning that all participants eventually received all the different ddI doses during the study in both the fasted state (days 1 and 3) and with tenofovir and food (days 10, 12 and 14). This design means that many more time points were available for measurement of ddI levels. Tenofovir was dosed with a meal of 373 kcal (68% carbohydrate, 20% fat and 12% protein).
When compared to the 400mg ddI dose, ddI 250mg dosed with tenofovir and food did not result in a significantly lower drug exposure as measured by AUC, whilst the 325mg dose resulted in slightly higher drug exposure. However, ddI peak levels (Cmax) were lower when dosed with tenofovir and food, by approximately 11 to 20%, and the half-life of the drug increased by around 40%.
The two drugs were generally well tolerated, with all adverse events reported during the tenofovir-only dosing phase (nausea was reported by 22.9%, vomiting by 11.4% and rash by 11.4%).
Kaul S et al. Pharmacokinetic evaluation of reduced doses of didanosine enteric coated capsules (ddI EC) in combination with tenofovir disoproxil fumarate (TDF) and food a for a once daily antiretroviral regimen. 4th International Workshop on Clinical Pharmacology of HIV therapy, abstract 54, 2003.