A pharmacokinetic evaluation of 0.5% and 5% fluorouracil topical cream in patients with actinic keratosis

Abstract Background: Systemic absorption of topical fluorouracil, although usually low, may vary as a result of the specific skin disease, product formulation, and other factors. Objective: The present study was conducted to determine the pharmacokinetic profile and tolerability of a new topical 0.5% fluorouracil cream formulation compared with that of a currently available topical formulation of 5% fluorouracil cream. Methods: This was an open-label, parallel-group study in which patients with actinic keratosis (AK) were randomized to treatment with either topical 0.5% fluorouracil once daily or topical 5% fluorouracil twice daily for up to 28 days. Results: Twenty-one patients (all white; mean age, 64 years) participated in the study, 11 receiving topical 0.5% fluorouracil and 10 receiving topical 5% fluorouracil. Ten patients receiving 0.5% fluorouracil and 7 patients receiving 5% fluorouracil completed the 28-day study. Plasma concentrations of fluorouracil were detectable in 3 of 10 patients treated with 0.5% fluorouracil and 9 of 10 patients treated with 5% fluorouracil; fluorouracil was detected in the urine of 5 and 9 patients, respectively. Despite the one-tenth difference in drug concentration between formulations, the cumulative amount excreted in the urine of the 0.5% fluorouracil group was approximately one fortieth that of the 5% fluorouracil group. This difference may be a result of variations in vehicle formulations. At least 1 adverse event was reported by 4 of 11 patients in the 0.5% fluorouracil group and all 10 patients in the 5% fluorouracil group. The most common adverse event, facial irritation, was evident with both formulations but reached a plateau during treatment with 0.5% fluorouracil. All patients treated with 0.5% fluorouracil tolerated the full course of therapy, whereas 3 patients in the 5% fluorouracil group discontinued treatment early. No serious treatment-related adverse events were reported. Conclusions: These data suggest that 0.5% fluorouracil has minimal systemic absorption and is well tolerated in patients with AK.