HIV Treatment Bulletin - Vol. 7, No. 6, June 2006
Simon Collins, HIV i-Base

Girard and colleagues from St Antoine Hospital, Paris, presented data on intracellular (IC) levels of ddA-TP, the active metabolite of ddI, under fed and fasted conditions. Plasma concentrations of ddI are reduced by 17-28% when taken with food, and ddI is therefore recommended to be taken on an empty stomach and two hours before food. This randomised cross-over study in 24 patients with viral load <200 copies/mL on ddI/EC-containing regimens before food (fasted) and with a light meal.

ddA-TP levels were measured in 12 subjects (18 observations) and ddI levels were measured in 24 subjects (36 observations). Irrespective of food status, the IC ddA-TP PK profile was flat, in contrast to the peak and valley observed in the plasma ddI PK profile. Summary statistics for ddI and ddA-TP PK parameters show a 23% reduction in IC ddA-TP AUC, and a 34% reduction in plasma ddI exposure when ddI was dosed with food. All patients maintained viral suppression during the study.

The study concluded that plasma ddI and IC ddA-TP levels were reduced when ddI was dosed with a light meal. The clinical relevance of this food effect remains unclear.

Comment

Given that ddI is generally used in patients with some NRTI-resistance, and is often a component of regimens in multiple drug experienced patients, achieving optimal concentration is these patients will be important.

The flat IC exposure curve, together with long half-life of ddI suggests that observing fasted administration is probably more critical than exact time of dosing. Given the difficulties associated with fasted dosing, this may be useful for patient to consider, in situations when they may have eaten: delaying dosing for two hours is likely to be better than dosing at the exact time with a meal.

Ref: Girard PM, Benech H, Gengron A et al. Food effect on the intracellular (IC) pharmacokinetics of Dideoxyadenosine Triphosphate (ddA-TP), the active metabolite of didanosine (ddI), in treated HIV-1 infected patients. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 79.

2006-06-10
IB060706-20

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