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 mm2 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 mm2 were enrolled. Day 21 mean (SD) serum Cmax was 0.49 (0.37) ng/mL, AUC0–24 6.80 (3.59) ng·h/mL, and t1/2 24.1 (12.4) hours. Steady state was achieved by day 7 with ∼2-fold increase in Cmax and AUC after multiple dosing. Overall, Cmax was higher and tmax shorter in women, with comparable AUC0–24. 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.