14th International AIDS Conference Barcelona, Spain — July 7-12, 2002

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. LbPeB9026

BACKGROUND: A previous PK study identified increases in ddI C_max and AUC (28% and 44%) when TDF and ddI (buffered tablets) were co-administered. The primary objective of this study was to evaluate whether ddI or tenofovir PK were affected by co-administration of ddI EC + TDF (ddI EC fasted followed by TDF 2 hrs later with a light meal (373 kcal, 20% fat)). A secondary objective was to investigate a 3-way interaction of simultaneous administration of ddI EC + TDF + a light meal as food interferes with ddI absorption.

METHODS: Healthy subjects received ddI EC 400 mg (days 1, 8, and 9) and TDF 300 mg QD with food (days 2-15). Blood samples were obtained over 24 hr on days 1, 8, 9 and 15. PK parameters were calculated using noncompartmental methods. Statistical tests included generation of 90% confidence intervals (CI) for the ratio of geometric means [GMR (90% CI)] for tenofovir and ddI AUC and C_max given together vs. alone.

RESULTS: ddI EC had no effect on the PK of tenofovir (GMR 90% CI within 80 to 125%). ddI systemic exposures were increased by 48% when dosed in a fasted state, two hours before TDF with a light meal [AUC0-„V 1.48 (1.31, 1.67); C_max 1.48 (1.25, 1.76)]. ddI exposures were similarly elevated when ddI EC was given simultaneously with TDF and a light meal [AUC0-„V 1.60 (1.44, 1.79); C_max 1.64 (1.41, 1.89)].

CONCLUSIONS: Administration of ddI EC 2 hours prior to or simultaneous with TDF and a light meal resulted in elevated ddI exposures relative to ddI EC alone in the fasted state. Further evaluations, including considerations of dosage adjustment for ddI EC, are warranted.

Presenting author: AK Cheng

1 Gilead Sciences, Foster City, CA, United States

020708
LbPeB9026

Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.