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 C(max) was 0.49 (0.37) ng/mL, AUC₀₋₂₄ 6.80 (3.59) ng·h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with ~2-fold increase in C(max) and AUC after multiple dosing. Overall, C(max) was higher and t(max) 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.
Graceway Pharmaceuticals, LLC, Exton, Pennsylvania, USA. jasonwu.md@gmail.com
Jason
J
Wu
Robert
R
Feldman
Gabrielle T
GT
Barry
James
J
Kulp
Michael P
MP
Adams
Sharon
S
Levy
D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001004:Anus Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D001711:Biotransformation; D003218:Condylomata Acuminata / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003875:Drug Eruptions / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006119:Groin; D006207:Half-Life; D006801:Humans; D000077271:Imiquimod; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D009824:Ointments; D010502:Perineum; D012646:Self Administration; D012720:Severity of Illness Index; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors*; D014860:Warts / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D055815:Young Adult
D000634:Aminoquinolines; D007155:Immunologic Factors; D009824:Ointments; D051199:Toll-Like Receptor 7; D000077271:Imiquimod