Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children.
BACKGROUND
Tacrolimus is a potent immunosuppressant used in organ transplant recipients; an ointment formulation is being developed as a therapeutic agent for atopic dermatitis.


OBJECTIVE
Our purpose was to define the pharmacokinetics and evaluate tacrolimus 0.3% ointment as therapy for moderate to severe atopic dermatitis.


METHODS
Thirty-nine patients, 5 to 75 years of age, received 14 applications over 8 days. Serial blood samples were collected on days 1 and 8, with predose samples collected on days 2 through 7. Overall response and signs/symptoms were rated daily on days 1 through 11. Incidence of adverse events and laboratory profile were determined.


RESULTS
Mean area under the curve (0.9 to 42.5 ng x hr/ml) was highly variable and appeared to be related to size of application area. No systemic accumulation of tacrolimus was observed. Comparison to historical intravenous data indicates that absolute bioavailability of topical tacrolimus was less than 0.5%. Ninety-five percent of patients showed at least good improvement. All adverse events were transient. Burning was the most common application site adverse event and vasodilatation ("flushing/warmth") was the most common nonapplication site adverse event. No drug-related changes in laboratory profile were observed.


CONCLUSIONS
The results of this study suggest that tacrolimus 0.3% ointment may be a safe and effective therapy for atopic dermatitis.
Alaiti
S
S
Department of Dermatology, University of Illinois at Chicago, 60612, USA.
Kang
S
S
Fiedler
V C
VC
Ellis
C N
CN
Spurlin
D V
DV
Fader
D
D
Ulyanov
G
G
Gadgil
S D
SD
Tanase
A
A
Lawrence
I
I
Scotellaro
P
P
Raye
K
K
Bekersky
I
I
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D005260:Female; D005483:Flushing / Q000139:chemically induced; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015994:Incidence; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009824:Ointments; D012074:Remission Induction; D012678:Sensation Disorders / Q000209:etiology; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects
D007166:Immunosuppressive Agents; D009824:Ointments; D016559:Tacrolimus