Tacrolimus Ointment does not Affect Collagen Synthesis: Results of a Single-Center Randomized Trial

• Published in: Journal of investigative dermatology Vol. 111; no. 3; pp. 396 - 398
• Main Authors: Reitamo, Sakari, Rissanen, Jonna, Remitz, Anita, Granlund, Håkan, Erkko, Pekka, Autio, Pekka, Lauerma, Antti I., Elg, Peter
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-09-1998; Nature Publishing
• Subjects: Adolescent; Adult; atrophy; Biological and medical sciences; Collagen - biosynthesis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - metabolism; Double-Blind Method; Female; Humans; Immunomodulators; Immunosuppressive Agents - therapeutic use; Male; Medical sciences; Middle Aged; Ointments; Peptide Fragments - metabolism; Pharmacology. Drug treatments; PICP; PINP; Procollagen - metabolism; Reference Values; skin; Tacrolimus - therapeutic use; atrophy; skin; PICP; PINP; Human; Local administration; Tacrolimus; Collagen; Skin; Immunosuppressive agent; Experimental study; Biological activity; Topical administration
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.1998.00323.x

We conducted a randomized, double-blind, placebo-controlled trial to assess the atrophogenicity of tacrolimus ointment. In a combined group of atopic dermatitis patients (n = 14) and healthy volunteers (n = 12), 0.3% tacrolimus, 0.1% tacrolimus, betamethasone-valerate, and a vehicle control were applied in a randomized order to nonsymptomatic, 4 cm × 4 cm regions of abdominal skin. After 7 d of treatment under occlusion, the carboxy- and amino-terminal propeptides of procollagen I (PICP, PINP) and the amino-terminal propeptide of procollagen III (PIIINP) were measured from suction blister fluid with specific radioimmunoassays. In addition, ultrasound measurements of skin thickness were taken. Betamethasone-treated areas showed median PICP, PINP, and PIIINP concentrations of 17.0%, 17.6%, and 39.5% of the vehicle control at the end of the treatment period, respectively, whereas the 0.1% and 0.3% tacrolimus-treated areas showed median concentrations of ≈100% of the vehicle control (p < 0.001). Betamethasone was also the only treatment to reduce skin thickness; the median decrease in skin thickness was 7.4% relative to 0.1% tacrolimus, 7.1% relative to 0.3% tacrolimus, and 8.8% relative to the vehicle control (p < 0.01). Results for atopic dermatitis patients and healthy volunteers were similar. These findings suggest that tacrolimus does not cause skin atrophy.