Although the following is not specific to dogs, we thought it useful in presenting some of the differences between the two drugs.
Topical Tacrolimus
S.J. Frankel, BSc and F.A. Kerdel, BSc, MBBS, MD
Departments of Dermatology & Cutaneous Surgery,
University of Miami School of Medicine, Miami, Florida, USA
ABSTRACT
Tacrolimus, available for intravenous, oral and now topical administration, is a potent immunosuppressive agent with the
ability to block the production of Interleukin-2 (IL-2) and inhibit T-cell proliferation. Originally developed for use in organ
transplantation, it is currently being studied for the treatment of inflammatory dermatoses. The US FDA recently approved
tacrolimus ointment (Protopic, Fujisawa) for the treatment of atopic dermatitis.
KEY WORDS: tacrolimus, atopic dermatitis, immunosuppressant
Tacrolimus, previously known as FK506, is an 822-KDa-macrolide
antibiotic produced by the fungus Streptomyces
tsukubaensis. It is a powerful immunosuppressant and although
it’s not structurally related, tacrolimus exhibits selective
antilymphocytic activity similar to cyclosporine, an agent that has
revolutionized transplantation medicine and the treatment of
selected autoimmune disorders. Currently, tacrolimus is emerging
as a promising therapeutic alternative for the treatment of a
number of dermatological diseases that have in common an
aberrant immunologic response. This topical ointment is the first
of its kind to be approved by the US FDA (December 2000),
0.1% for the treatment of moderate-to-severe atopic dermatitis in
adults, and 0.03% for children older than 2 years of age and for
adults who are undergoing long-term intermittent therapy. Phase
III trials are underway in Canada, where a New Drug Submission
(NDS) was put forward in July 2000. In Japan, Protopic 0.1%
was approved in 1999.
MECHANISM OF ACTION
Both tacrolimus and cyclosporine interrupt the T-cell receptor
mediated signal transduction pathway, which ultimately blocks
the production of Interleukin-2 (IL-2) and inhibits T-lymphocyte
proliferation. However, in vitro studies have shown that when
compared to cyclosporine, tacrolimus exhibits 10-100 times
greater immunosuppressive activity.1
Unlike cyclosporine, a molecule which seems to be too large to
penetrate human skin, tacrolimus is active topically and appears
to target epidermal leukocytes, and antigen presenting epidermal
dendritic cells.
PHARMACOKINETICS
When applied to intact human skin, in vitro studies have
demonstrated that tacrolimus is not readily absorbed. However, on
inflamed or damaged skin, it is absorbed in sufficient amounts to
be topically active. The agent is metabolized in the liver by
Cytochrome P4503A4 and is eliminated almost completely in the
bile.1,3,5
INDICATIONSs
Perhaps most exciting is the finding that topical preparations of
tacrolimus, in contrast to cyclosporine, are effective for the
treatment of certain skin disorders including atopic dermatitis and
allergic contact dermatitis.