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Pharmacokinetics of imiquimod 3.75% cream applied daily for 3 weeks to actinic keratoses on the face and/or balding scalp

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Abstract

Imiquimod 3.75% cream is a topical formulation of imiquimod intended for daily application to treat actinic keratoses of the entire face or balding scalp. The objective of the study was to characterize serum imiquimod and metabolite pharmacokinetics. Nineteen subjects with actinic keratoses applied two packets of imiquimod 3.75% cream (18.75 mg imiquimod total) once daily for 21 days to a treatment area approximately 200 cm2 in size on the face and/or balding scalp. Blood samples were obtained prior to application of doses 1, 7, 14 and 21, and at selected timepoints after application of doses 1 and 21. After multiple dosing (day 21) serum imiquimod mean C max was 0.323 (standard deviation 0.159) ng/mL, mean AUC(0-24) 5.974 (3.088) ng h/mL, and mean T½ 29.3 (17.0) h. Steady-state was achieved by day 14; multiple dose accumulation ratios were 2.8 based on imiquimod C max and 3.9 based on AUC. Serum concentrations of imiquimod metabolites were only sporadically quantifiable in three subjects. One subject discontinued from study for adverse events of body aches and fatigue that were attributed to study drug. Treatment-related adverse events occurred in 42.1% (8/19) of the subjects. Systemic imiquimod exposure, as reflected by serum drug concentration, was low after daily application of two packets of imiquimod 3.75% cream for 21 days. Steady state was achieved by day 14, and the observed half-life of approximately 29 h supports daily dosing of the product.

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Abbreviations

AK(s):

Actinic keratosis(es)

AE(s):

Adverse event(s)

AUC:

Area under the serum concentration versus time curve

C max :

Maximum serum concentration

LLOQ:

Lower limit of quantitation

LSR(s):

Local skin reaction(s)

PK:

Pharmacokinetic

T½EFF:

Effective half-life for accumulation

T½:

Half-life

T max :

Time of C max

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Acknowledgments

The authors would like to acknowledge Dr. Shari Skinner for her assistance in dermatological assessments of the subjects, and Bao Chen for assistance with statistical analyses. This study was funded by Graceway Pharmaceuticals LLC, Bristol, Tennessee.

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Authors and Affiliations

  1. Graceway Pharmaceuticals LLC, 222 Valley Creek Blvd, Suite 300, Exton, PA, 19341, USA

    James Kulp, Sharon Levy & Tze-Chiang Meng

  2. Comprehensive Phase One, Fort Myers, FL, USA

    Melanie C. Fein

  3. MPA Consult, LLC, Kennett Square, PA, USA

    Michael Adams

  4. Furst Pharmaceutical Services Inc., Schwenksville, PA, USA

    John Furst

Authors
  1. James Kulp
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  2. Sharon Levy
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  3. Melanie C. Fein
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  4. Michael Adams
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  5. John Furst
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  6. Tze-Chiang Meng
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Correspondence to Tze-Chiang Meng.

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Kulp, J., Levy, S., Fein, M.C. et al. Pharmacokinetics of imiquimod 3.75% cream applied daily for 3 weeks to actinic keratoses on the face and/or balding scalp. Arch Dermatol Res 302, 539–544 (2010). https://doi.org/10.1007/s00403-010-1041-8

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  • DOI: https://doi.org/10.1007/s00403-010-1041-8

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