Search

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., Conclusion: The results of this study suggest that tacrolimus 0.3% ointment may be a safe and effective therapy for atopic dermatitis.

A rat model for studying causes of body fat accretion was developed. Employing this model, it was possible to produce a 108 g difference in carcass fat content between two groups of rats simply by selecting the seven fattest and the seven leanest animals from a group of 100. The results of this study provide evidence that the gastrointestinal tract was not a site of caloric wastage, that total energy excreted in feces and urine was directly proportional to caloric intake, that differences in brown adipose tissue thermogenesis were not responsible for the twofold difference in adiposity between the lean and fat rats, and that a family of hepatic lipogenic enzymes was not up-regulated even though the habitual consumption of a diet rich in carbohydrate was greater in the fat vs lean rats. The fat rats also had a greater lean body mass. Therefore, the additional calories consumed by the fat rats could have contributed to their greater adiposity and/or could have been channeled to sustain more active tissue. Finally, evidence was presented to show that the experimental selection process is an important consideration when determining the relationship between caloric intake and body fat content.