title: Occlusive treatment of chronic hand dermatitis with pimecrolimus cream 1% results in low systemic exposure, is well tolerated, safe, and effective. An open study.
abstract: BACKGROUND
  Pimecrolimus cream 1% (Elidel, SDZ ASM 981) is a novel, non-steroid inflammatory cytokine inhibitor, effective in the treatment of atopic dermatitis. Here, we evaluate the treatment of chronic hand dermatitis with pimecrolimus cream 1%.
  
  
  OBJECTIVE
  To determine pimecrolimus blood concentrations, and evaluate the safety, tolerability and efficacy following application of pimecrolimus cream 1% to subjects with chronic hand dermatitis.
  
  
  METHODS
  In this open-label, multiple-topical-dose, non-controlled, pharmacokinetic study, pimecrolimus cream 1% was applied twice daily to dorsal and palmar areas (affected and unaffected) of both hands. Evening applications (except day 8) were immediately followed by overnight occlusion (> or =6 h). Full pharmacokinetic profile (days 1, 8 and 22), trough concentrations (days 3 and 15), physical examinations, laboratory measurements and adverse events were recorded. Efficacy was assessed via Investigators' Global Assessment (IGA), total key signs and symptoms and the subject's overall self-assessment.
  
  
  RESULTS
  Twelve patients completed the study. The majority of pimecrolimus blood concentrations (73.6%) remained below the limit of quantitation (0.1 ng/ml). The maximum concentration observed was 0.91 ng/ml and the maximum area under the concentration-time curve from 0-12 h post dose was 7.6 ng.h/ml. Treatment was well tolerated locally and systemically. No serious adverse events occurred; 4/13 subjects showed a total of 6 adverse events at the application site: burning (n=4), and pruritus (n=2). No clinically relevant or drug-related changes were observed. Clear efficacy of the treatment was shown by all 3 assessment methods. Disease state at day 22 had improved in 11 (85%) subjects compared with baseline (IGA).
  
  
  CONCLUSIONS
  Twice daily topical treatment of moderate to severe chronic hand dermatitis with pimecrolimus cream 1% results in low pimecrolimus blood levels, is well tolerated, safe, and effective.
authors.affiliation: Department of Dermatology and Venereology, J.-W. Goethe University School of Medicine, Frankfurt, Germany. thaci@em.uni-frankfurt.de
authors.forename: Diamant
authors.initials: D
authors.lastname: Thaçi
authors.forename: Katrin
authors.initials: K
authors.lastname: Steinmeyer
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Ebelin
authors.forename: Graham
authors.initials: G
authors.lastname: Scott
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
mesh_terms: D000287:Administration, Topical; D000328:Adult; D001682:Biological Availability; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006229:Hand Dermatoses / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009824:Ointments; D016559:Tacrolimus / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009824:Ointments; C117268:pimecrolimus; D016559:Tacrolimus