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Archives of Dermatological Research

, Volume 296, Issue 1, pp 6–11 | Cite as

Pharmacokinetics and safety of imiquimod 5% cream in the treatment of actinic keratoses of the face, scalp, or hands and arms

  • Lester I. HarrisonEmail author
  • Shari L. Skinner
  • Thomas C. Marbury
  • Mary L. Owens
  • Sarala Kurup
  • Scott McKane
  • Robert J. Greene
Original Paper

Abstract

The safety and efficacy of imiquimod 5% cream is being evaluated for the treatment of dysplastic lesions of the epidermis (actinic keratoses, AK). The objective of this clinical study was to describe the pharmacokinetics and safety of topical imiquimod during multiple dosing of AK subjects. A total of 58 adult subjects with 5 to 20 AK lesions at the treatment site applied imiquimod cream three times per week for up to 16 weeks as follows: 12 males and 11 females applied 12.5 mg imiquimod to the face; 11 males applied 25 mg to the entire balding area of the scalp; and 12 males and 12 females applied 75 mg to both hands and forearms. Pharmacokinetics and safety were assessed after the first and last doses, as well as biweekly. Imiquimod and its metabolites were measured in the serum and urine using sensitive liquid chromatography/mass spectrometry methods. Less than 0.6% of the applied doses was recovered in the urine of all subjects. Serum imiquimod levels were low, reflecting minimal dermal absorption, and increased with dose, although not proportionally. Peak levels at the end of dosing were 0.1, 0.2, and 1.6 ng/ml for the face, scalp, and hands/arms groups, respectively. A two- to fourfold accumulation was seen at the end of dosing. Local application site reactions were the most common adverse event, reported by approximately 50% of the subjects in each treatment group. The small number of systemic adverse events, including ‘flu-like symptoms, were mostly mild and did not show a dose response. Thus, minimal systemic absorption and good safety margins for topical imiquimod were seen in AK subjects with doses as high as 75 mg three times per week for 16 weeks.

Keywords

Actinic keratosis Imiquimod Immunomodulator Pharmacokinetics Safety 

Abbreviations

AK

Actinic keratosis

2,5-AS

2′5′-Oligoadenylate synthetase

AUC

Area under the concentration-time curve

Cmax

Maximum serum concentration

IFN

Interferon-alpha

IL-1RA

Interleukin-1 receptor antagonist

Rmax

Maximum change from baseline value

Notes

Acknowledgements

The authors would like to acknowledge the following individuals who contributed to this study report: Sharon Parrish, Nanda Gosala, Jim Lee, Bruce Ekholm, Adele Hoglin, Paula Myhre, Sagar Kawle, Anthony Pierce, Kirsten Watne and Debra Kielhold from 3 M Pharmaceuticals; Simone Jones from SFBC Fort Myers; and Tammy Johnson from Orlando Clinical Research Center. This study (1402-IMIQ) was sponsored by 3 M Pharmaceuticals.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Lester I. Harrison
    • 1
    Email author
  • Shari L. Skinner
    • 2
  • Thomas C. Marbury
    • 3
  • Mary L. Owens
    • 4
  • Sarala Kurup
    • 1
  • Scott McKane
    • 4
  • Robert J. Greene
    • 1
  1. 1.Department of Pharmacokinetics and Drug Metabolism3 M PharmaceuticalsSt. PaulUSA
  2. 2.SFBC Fort Myers IncFort MyersUSA
  3. 3.Orlando Clinical Research CenterOrlandoUSA
  4. 4.Department of Medical Affairs3 M PharmaceuticalsSt. PaulUSA

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