Effect of food on the pharmacokinetics and bioavailability of oral imiquimod relative to a subcutaneous dose

Objectives: The present study, the first clinical pharmacokinetic report of the immune response modifier imiquimod, was conducted to assess the effect of food on the oral absorption of imiquimod, to characterize its pharmacok inetics, and to estimate its oral bioavailability. Subjects and methods: Si xteen healthy male volunteers completed this open-label, randomized, three- period crossover study. Subjects received a 100 mg oral dose of imiquimod a fter fasting in one period, after a standarized, high fat meal in another, and a 30 mg subcutaneous dose in the third period. Results: The oral bioava ilability of imiquimod was on average 47%, and independent of whether imiqu imod was administered with or without food. Oral imiquimod was absorbed in both fasted and non-fasted states with an absorption half-life of approxima tely 1 hour. However, there seemed to be a delay in the initiation of the a bsorption process when food was administered, which translated in to a T-ma x of approximately 2.6 hours while fasting and one hour later in the non-fa sted state. Imiquimod was rapidly eliminated with a half-life of approximat ely 2.5 hours and a total body clearance of approximately 970 ml/h x kg. Al though equivalence could not be established due to the large intersubject v ariability, no significant differences in rate (C-max) and extent (AUC) of oral absorption were observed between the fasted and non-fasted states. In addition, the C-max, AUC and bioavailability values for individual subjects were consistent between both oral treatments. Conclusion: This study sugge sts that food does not have a major effect on the rate, extent of absorptio n or bioavailability of oral imiquimod, and thus, it is suitable to adminis ter imiquimod orally in either the fasted or non-fasted states.