Pharmacokinetics of daily self-application of imiquimod 3.75% cream in adult patients with external anogenital warts.

Imiquimod 3.75% cream is a new formulation intended for daily self-application. The objective of this study was to characterize serum imiquimod pharmacokinetics under maximal use conditions. Adults with >= 8 warts or total wart area >= 100 mm(2) applied up to 1 packet of imiquimod 3.75% cream (250 mg cream, 9.375 mg imiquimod) once daily for 3 weeks. Blood was obtained prior to doses 1, 7, 14, and 21 and at selected time points after doses 1 and 21. Eighteen patients (13 men and 5 women) with a median wart count of 16 and total wart area of 60 mm(2) were enrolled. Day 21 mean (SD) serum C-max was 0.49 (0.37) ng/mL, AUC(0-24) 6.80 (3.59).ng.h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with similar to 2-fold increase in C-max and AUC after multiple dosing. Overall, C-max was higher and t(max) shorter in women, with comparable AUC(0-24). Imiquimod metabolites were sporadically quantifiable. No patients discontinued for adverse events; 1 interrupted dosing for an application site ulcer. Treatment-related adverse events occurred in 16.7% of the patients. In conclusion, serum imiquimod concentrations were low after daily self-application to external anogenital warts of up to 1 packet of imiquimod 3.75% cream for 21 days.