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Veterinary Dermatology 2002, 13, 203 210

Blackwell Science, Ltd

Investigation on the use of 0.3% tacrolimus lotion for canine

atopic dermatitis: a pilot study
ROSANNA MARSELLA and CONSTANCE F. NICKLIN
College of Veterinary Medicine, Department of Small Animal Clinical Sciences, University of Florida,
Gainesville, FL, USA
(Received 6 September 2001; accepted 20 March 2002)

Abstract The efficacy of 0.3% tacrolimus lotion (maximum dosage: 0.3 mg kg1 per day) for treatment of atopic
dermatitis (AD) was evaluated. Systemic absorption and effects on complete blood cell counts (CBC) and
chemistry panels were also investigated. Eight dogs were assigned randomly to either a tacrolimus or a vehicle
lotion treatment group. Both owners and investigator were blinded to the treatment. After 4 weeks, there was a
2-week wash-out period and treatments were reversed. Owners scored pruritus weekly while the investigator
scored pruritus and erythema at the beginning and end of each treatment period. Investigator scores for pruritus
in the tacrolimus group significantly decreased by the end of the study (P = 0.03). Investigator scores for erythema
in the tacrolimus group were significantly lower than those in the placebo group at the end of the study
(P = 0.005). There was no difference between groups with respect to owner scores for pruritus. No changes in
the CBC and chemistry panels were noted. Mean blood concentrations of tacrolimus were below toxic levels.
Keywords: atopic dermatitis, canine, FK-506, tacrolimus.

INTRODUCTION
Canine atopic dermatitis is a common and frustrating
problem in veterinary dermatology. Atopic dermatitis
(AD) is the second most common allergy in dogs (10%
of canine population).1 Despite the fact that AD is
common, the understanding of the pathogenesis of this
disease and the therapeutic options available for the
affected animals are limited. Systemic treatments like
glucocorticoids and cyclosporin are quite effective2 but
have the potential for serious adverse effects.3 Antihistamine therapy may be used but the success rate is
often unsatisfactory.1 Hyposensitization is used in
some patients, however clinical improvement is usually
not seen for the first 69 months of therapy. Finally, all
of the currently available topical agents provide only
partial and temporary relief of symptoms. Thus the
identification of a safe, fast-acting and highly effective
topical treatment in canine AD would be of tremendous
benefit.
Tacrolimus (FK-506) is a macrolide lactone produced by the fungus Streptomyces tsukubaensis and is
chemically distinct from cyclosporin A, yet has similar
activity.4 Topical tacrolimus was approved for use in
humans with AD in Japan in November 1999 and was
launched on the US market in 2001. Tacrolimus
inhibits the T lymphocyte response to antigens and the
Correspondence:
Rosanna
Marsella,
Blanche
Saunders
Dermatology Laboratory, Department of Small Animal Clinical
Sciences, University of Florida, College of Veterinary Medicine, P.O.
Box 100126, Gainesville, FL 32610 0126. Tel: +1 352 392 4700 ext.
5277; Fax: +1 352 392 6125; E-mail: MarsellaR@mail.vetmed.ufl.edu
2002 Blackwell Science Ltd

production of the cytokines responsible for T cell

proliferation (Interleukin-2).5 Tacrolimus achieves this
by forming a complex with a cyclophilin-like protein
(FKBP12), and this complex, in turn, inhibits the ability of calcineurin to dephosphorylate the transcription
factor required for the activation of IL-2 and IL-4 gene
transcription.5 Tacrolimus also inhibits other T cellderived cytokines, such as IL-3, IL-4, IFN- and TNF-
that contribute to allergic inflammation.5,6 In addition
to lymphocytes, tacrolimus down-regulates cytokine
expression in other cells that have tacrolimus binding
proteins and that are important in allergic skin inflammation. These include mast cells, basophils, eosinophils,
keratinocytes and Langerhans cells.79 Topical tacrolimus leads to profound phenotypic and functional
alterations of epidermal antigen-presenting dendritic
cells in patients with AD and down-regulates the expression of the high-affinity IgE receptor (FcepsilonRI) in
Langerhans cells.10 Tacrolimus inhibits the expression
of IL-2R (CD25), the costimulatory molecules CD80
(B7.1) and CD40, and both classes of MHC.11
A significant advantage of tacrolimus over cyclosporin
is its efficacy after topical application.12 This difference
between tacrolimus and cyclosporin is due to tacrolimus
smaller molecular weight and its greater ability to
permeate the skin.13 Tacrolimus is therefore a powerful
topical immunomodulator that can effectively decrease
inflammation and allergic reactions.
Topical tacrolimus has been used successfully to
decrease signs of AD in humans, both adults and
children.1416 Clinical improvement is marked and
rapid and appears to be directly proportional to the
concentrations used.17 A mean percentage improvement
203

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204

R. Marsella and C. F. Nicklin

of 83% of clinical scores was reported with 0.1%

ointment and a significant difference from placebo was
evident as early as day 8.18 When a 0.3% ointment was
used, improvement of clinical lesions was observed
on day 3 in 81% of the adult patients and 88% of the
children.19 By day 8, clinical improvement was evident
in 94% of the adults and 100% of the children.19
Despite its potency, topical tacrolimus is safe and
minimally absorbed.1519 Tacrolimus ointment (0.3%)
was applied to up to 30% of the total body surface area
of adults and children and the highest blood level of
tacrolimus was 1.6 ng mL1, which is substantially
below concentrations (> 20 ng mL1) that have been
associated with an increased risk of toxicity.20 The
bioavailability of topically applied tacrolimus was
calculated to be less than 0.5% relative to intravenous
administration.19 Also, with repetitive applications, no
significant accumulation was found.18,19 Adverse effects
were minor and self-limited.1419 The most common
adverse effects were a burning sensation and erythema.
However, these symptoms occurred equally in both
the vehicle and tacrolimus groups, and none of them
occurred after the first 3 days of treatment, despite
uninterrupted drug applications. No significant changes
in laboratory profile have been associated with the
administration of tacrolimus ointment.1619,21
It is also believed that tacrolimus may have some
self-regulatory activity that could be beneficial for its
safety.22 Its molecular weight (823 Da) is such that it
can penetrate inflamed skin, but it hardly penetrates
the epidermis of normal skin. Once inflammation is
decreased, it is hypothesized that the compound will
penetrate less, limiting the risk of adverse effects. The
fact that the burning sensation rapidly decreases with
the improvement of the skin lesions seems to support
this hypothesis. Thus, the efficacy and safety of topical
tacrolimus make this drug one of the most promising
therapeutic options currently available for patients
with AD and could have a great potential for canine
allergies.
Pharmacokinetic parameters of tacrolimus have
been evaluated in dogs.23,24 After oral administration,
absorption is quite variable and not dependent on the
presence of bile. Tacrolimus distributes throughout the
body and undergoes extensive metabolism by the P450
microsomal enzyme system. Tacrolimus binds primarily to albumin in plasma and is mainly associated with
erythrocytes in whole blood. Elimination is via the
biliary route, mainly as metabolites. Tacrolimus has been
administered both intramuscularly and intravenously
to dogs for allotransplantation.23,2527 At high doses
(24 mg kg1) adverse effects (e.g. weight loss, vomiting and diarrhea) were noted, while at 0.1 mg kg1 no
adverse effects were reported.23 At the present time
there is no published information available on the topical use of tacrolimus in dogs. At the time of the study
tacrolimus was not available as topical treatment, but
since then it has been approved by the FDA and is
available on the market as an ointment (Protopic,
Fujisawa, Deerfield, IL, USA). The purpose of this
2002 Blackwell Science Ltd, Veterinary Dermatology, 13, 203 210

pilot study was to investigate the efficacy and safety of

0.3% tacrolimus lotion in dogs with AD.

MATERIALS AND METHODS

In order to test the hypotheses a randomized, double
blind, placebo controlled, crossover clinical study was
designed.
Animals
Eight dogs with naturally occurring AD were selected.
Inclusion criteria These were a diagnosis of AD, based
on suggestive history, compatible clinical signs, and at
least three positive reactions on intradermal skin testing using a panel of 57 allergens. A positive reaction
was considered a reaction that scored 2 or higher on a
scale from 0 to 4, where 0 was the score given to the
negative control (saline) and 4+ was the score of the
positive control (histamine) 15 min after the injections.
Exclusion criteria These were the presence of other
pruritic skin diseases (e.g. food allergy and scabies) and
the presence of secondary ear and skin infections (e.g.
staphylococcal pyoderma and Malassezia dermatitis).
Other exclusion criteria were the use of topical, oral
steroids and antihistamines in the 2 weeks prior to the
study and injectable steroids in the 2 months prior to
the study. During the study only heartworm prevention
and flea control [monthly application of Frontline
(Merial Limited, Iselin, NJ)] were allowed. Animals
with a pre-existing systemic disease or animals that
could not suspend therapy due to exceptional severity
of AD were excluded.
Experimental design
Selected dogs were divided into two equal groups.
Assignment to treatment was randomized by coin toss,
in that a coin toss prior to enrolling the first dog determined the treatment of that first dog. The remaining
dogs were enrolled in alternating treatments until all of
the dogs were enrolled. This allowed for equal distribution of dogs assigned to each treatment and minimized
order of treatment effects. The pharmacy compounded
both lotions to look identical and coded them A or
B. The code was not revealed until the study was completed. Neither owners nor investigators knew which
lotion was the treatment and which was the placebo
until the completion of the study.
Group A received 0.3% tacrolimus lotion once daily
(maximum dose of 0.1 mL kg1 per day, equivalent to
0.3 mg kg1 per day) on the areas owners felt were
most pruritic and Group B received a placebo lotion
(vehicle) for 4 weeks. The actual dose applied ranged
from 0.8 to 4.9 mL, with an average dose of 2.58 mL.
After the first 4 weeks there was a wash-out period of
2 weeks, and then the treatments were reversed, so
that Group A received placebo and Group B received
tacrolimus.

VDE_299.fm Page 205 Friday, July 26, 2002 4:10 PM

Tacrolimus for canine atopic dermatitis

Table 1. Criteria for evaluation and scoring
of erythema by the investigator

Table 2. Criteria for the evaluation and

scoring of pruritus by the investigator

Score

Definition

1
2
3
4
5

Mild erythema (barely visible, involving less than 10% of the body)
Mild to moderate erythema (noticeable, involving 1030% of the body)
Moderate erythema (easily noticeable, involving 3050% of the body)
Moderate-severe erythema (evident, involving 5075% of the body)
Severe erythema (evident, diffuse redness involving the entire body)

Score

Definition

1
2
3
4

No pruritus (no evidence of self-trauma)

Mild-moderate pruritus (15 mild excoriations, involving one part of the body)
Moderate pruritus (evident excoriations in more than one part of the body)
Moderate-severe pruritus (evidence of pyotraumatic dermatitis, or deep
ulcerations that are self-inflicted, or scratching, licking or chewing 15 times
during the visit)
Severe pruritus (scratching, chewing or licking constantly in the exam room,
self-mutilation if left unattended)

Table 3. Criteria for the evaluation and

scoring of pruritus by the owner

205

Score

Definition

1
2
3
4

Mild (scratching, rubbing, chewing or licking, <10% of day)

Mild-moderate (scratching, rubbing, chewing or licking, 1030% of day)
Moderate (scratching, rubbing, chewing or licking, 3050% of day)
Moderate-severe (scratching, rubbing, chewing, licking, 5075% of day,
still able to relax /sleep at night)
Severe (scratching, rubbing, chewing or licking all the time, even at night
and during a meal)

Concentrations and doses of tacrolimus were selected

based on studies performed in humans and on pilot
studies performed by the investigators in dogs with
AD (data not shown).15,18,19 In humans, the maximum
daily amount of tacrolimus used is 0.4 mg kg1 and
0.8 mg kg1.18,19 In pilot studies, doses of 0.6 mg kg1
and 0.9 mg kg1 (data not shown) were well tolerated.
Duration of the wash-out period was determined based
on the half-life of tacrolimus in dogs after systemic
administration (9 h).23,24
Tacrolimus lotion was prepared from capsules
(5 mg, Prograf, Fujisawa, Deerfiled, IL; provided at
cost by Barrier Island Pharmacy, Sanibel, FL) by a compounding pharmacy (Westlab Pharmacy, Gainesville,
FL, USA). The powder was wet with propylene glycol
and reduced to 0.3% in a lotion base containing 2:3
emollient cream and 1:3 preserved water. Each bottle
was used within 1 month of preparation.
Owners were instructed to wear gloves when applying the lotion. Dogs wore an Elizabethan collar or were
otherwise distracted until the lotion dried. No baths
were allowed 3 h before and after the administration of
the lotion. The investigator applied the first and last
treatments (week 0 and 4 of each treatment period).
Before and after each treatment, dogs received a
physical exam (PE), were evaluated for cutaneous
clinical signs, and blood was collected for CBC, chemistry
panel and determination of tacrolimus concentrations.
Dogs returned mid-treatment (week 2) for an additional
PE, CBC and chemistry panel. Owners were requested
to return the bottle of lotion at the completion of
each treatment period, which helped to verify owner

compliance. They were also asked to record on a data

sheet their weekly score of pruritus, and they returned
the data sheet at the end of each treatment period.
Clinical evaluation of efficacy
Erythema and pruritus were scored by the investigator
on weeks 0 and 4 of each treatment period using a scale
from 0 to 5, as previously described (Tables 1 and 2).28
A score for pruritus (scale of 05, with higher numbers
indicating more severe pruritus) was assigned by
owners weekly (Table 3).
Measurement of whole blood concentrations of
tacrolimus
On weeks 0 and 4 of each treatment period, immediately
before the lotion application (0 h), blood (10 mL) was
drawn from all dogs. Three millilitres were used for the
measurement of tacrolimus concentrations (heparinized
vacutainers, Becton Dickinson, Franklin Lakes, NJ,
USA) while the remaining blood (7 mL) was used for
CBC and chemistry panel (see below, Safety variables).
Additional blood samples (3 mL) were taken at 2, 4
and 6 h after lotion application for determination of drug
absorption. Samples to be used for tacrolimus measurement were stored at 20 C until analysis (stable for
6 months under these conditions). Whole blood concentrations of tacrolimus were measured using an enzymelinked immunosorbent assay (ELISA), as previously
described.29 The PRO-TRAC II Tacrolimus ELISA
Kit (DiaSorin, Stillwater, MN, USA) was used according
to the manufacturers recommendations. Blood concentrations, as opposed to plasma concentrations, of
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R. Marsella and C. F. Nicklin

tacrolimus were measured, as they correlate more closely

with immunosuppression and toxicity than the latter.30
The smallest quantity of tacrolimus detected by this
methodology was 0.27 ng mL1. Samples below the
detection limit were recorded as 0.15 ng mL1 in an
attempt to minimize over- or underestimation of the
actual value. Just because the value was below the detection limit does not mean that it was zero, but it does not
mean that it was exactly the detection limit either. It is
doubtful that the actual values were exactly zero or the
detection limit, so the average of the two was selected.
Safety variables
Safety was evaluated on the basis of incidence of
adverse effects and laboratory profile. CBC and chemistry panel profiles were determined at weeks 0, 2 and
4 of each treatment period.

Figure 1. Investigator clinical scores of pruritus. Indicates the

median.

STATISTICS
Data were analysed by least squares analysis of variance (LS) with all main effects and interactions
included in the model. Differences among treatments
and weeks were analysed using orthogonal contrast
analysis. Tests of heterogeneity of regression were
conducted to evaluate time trends between treatments.
The analysis was performed at the highest significant
order of regression, which was linear unless otherwise
stated. A value of P 0.05 was considered significant.
All data are presented as mean SEM (standard error
of the mean) unless otherwise indicated.
Because clinical scores are not normally distributed,
they were rank-transformed prior to analysis. Means
and SEM were calculated using the untransformed
data. However, all P-values are representative of the
rank-transformed data. All analyses were performed
using the statistical software package, The SAS System
for Windows, Version 8.1 (SAS Institute, Cary, NC).

Figure 2. Investigator clinical scores for erythema. Indicates the

median.

RESULTS
Results are based on seven dogs because one dog was
unable to complete the final treatment due to a severe
ear infection that required surgery. No differences were
detected between periods, indicating that order of
treatment did not have an effect, so data were pooled
and reanalysed without period in the model.
Investigator scores of pruritus
There was no difference in investigator pruritus scores
between treatments at weeks 0 or 4 (Fig. 1). Within the
tacrolimus group, week 4 was significantly lower than
week 0 (P = 0.0377). There were no differences within
the Placebo group.
Investigator scores of erythema
Investigator scores for erythema were not different
between the treatment groups at week 0, but by week 4
2002 Blackwell Science Ltd, Veterinary Dermatology, 13, 203 210

Figure 3. Owner clinical scores of pruritus over time. Indicates the

median.

erythema scores in the tacrolimus treatment group

were significantly lower when compared with the
placebo group (P = 0.01). There were no differences
within either treatment group (Fig. 2).
Owner scores of pruritus
There were no statistically significant differences in
owner scores for pruritus between treatments or within
treatment groups (Fig. 3).

VDE_299.fm Page 207 Friday, July 26, 2002 4:10 PM

Mean Tacrolimus Concentration (ng ml 1)

Tacrolimus for canine atopic dermatitis

5.00

Week 0

Week 4
*
*

4.50
4.00
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
0

6
0
2
Hour Post Treatment
Tacrolimus

Placebo

Figure 4. Concentration of tacrolimus in whole blood. *Indicates a

significant difference between weeks 0 and 4 within the treatment
group and at the time indicated. , tacrolimus; , placebo.

Tacrolimus concentrations
Tests for heterogeneity of regression revealed that
tacrolimus concentrations followed a cubic pattern,
and were therefore analysed at the 3rd order of regression (Fig. 4). Over all weeks and samples, there was no
difference between the placebo and tacrolimus groups.
Mean blood concentrations were below toxic levels,
however at week 4 two dogs had high blood concentrations (21.17 and 27.16 ng mL1), close to levels considered at increased risk for toxicity (> 20 ng mL1).
Within the tacrolimus treatment group, the week 42
and 4-h samples were significantly higher than those
times on week 0 (P = 0.018 and 0.031, respectively).
CBC and chemistry panel results
Over all times, there was no difference between treatments in all parameters.

DISCUSSION
In this pilot study, tacrolimus lotion at 0.3% was well
tolerated but only mildly effective. The investigator
noted a significant reduction of pruritus but none of
the dogs resolved completely by the end of the study.
The scores for erythema in the tacrolimus treatment
group were lower than the ones of the placebo group at
the end of the study but there was no statistically significant decrease of erythema in the tacrolimus group.
Thus the response to treatment in dogs was less marked
than what has been reported in humans, where
improvement was marked and rapid.1418 The difference in response might be due, in part, to the fact that
this pilot study used a lotion, while the human clinical
trials used an ointment.18,19 A lotion was used in this
study because it was thought that a lotion would be
easier to apply to the haircoat of a dog and, at the
time, there was no tacrolimus ointment commercially
available in the USA. Concerns were expressed by the
pharmacist regarding the stability of tacrolimus in a

207

water-based formulation and a tentative shelf life of

30 days was estimated. This is much shorter than the
2-year shelf life of the commercial ointment. It is
possible, therefore, that the water formulation might
have inactivated or decreased the efficacy of tacrolimus.
Unfortunately the measurement of the actual amount
of tacrolimus present in the lotion several weeks after
the lotion had been formulated was not taken. It is also
possible that the ointment has better penetration in the
skin. Since the end of this pilot study, one author (RM)
has tried the commercial ointment in a few atopic dogs
with localized pruritus, and a rapid successful response
was observed. It is not known whether this represents
individual variation, placebo effect or real efficacy. Future
placebo-controlled studies are therefore necessary
to evaluate a possibly different response to the ointment.
Another factor that may have influenced the results
of this trial was the fact that most of the dogs enrolled
had generalized pruritus. Due to concerns about possible systemic absorption and toxicity, a limited amount
of lotion (maximum daily amount of lotion for a 22 lb
dog was 1 mL) was allowed per day, and the lotion was
applied only once daily. The dose was selected based on
studies reported in human literature and was based on
a mg per kg basis.1419 The dose was calculated so that,
in the event of complete absorption, blood concentrations would have been below toxic levels. Based on the
results of this pilot study and of other studies done by
the author (RM) tacrolimus appears to be safe and
minimally absorbed in dogs. Thus, future clinical trials
should evaluate the efficacy of larger volumes of this
medication. Finally, it could be speculated that the
modest efficacy found in this clinical trial might be due
to differences in the pathogenetic mechanisms between
canine and human AD. Although differences exist
between the two species, numerous similarities have
also been reported, especially concerning the role of
Langerhans cells, subsets of T cells and cytokine
production.3133 Therefore, considering the broad spectrum of action of tacrolimus, the similarities between
human and canine AD, and the recently reported
efficacy of cyclosporin therapy in canine AD,2,34 the
moderate efficacy of tacrolimus reported in this study
is most likely due to the formulation and the dose used.
It is interesting to note that owners did not perceive
a significant improvement with tacrolimus while the
investigator did. This could be partly due to the fact
that animals have a suppressed pruritus while in a
stressful environment like hospital situation. It is thus
possible that the owner evaluation might have been a
more accurate assessment of the level of pruritus than
the one of the investigator.
Adverse effects in humans with topical tacrolimus
are minor and self-limited.1419 They are usually limited
to a temporary itching and burning sensation that
resolves spontaneously with continued use of the
medication. No systemic adverse effects have been
reported in humans, including children, using topical
tacrolimus. In our pilot study, tacrolimus was well
tolerated and no systemic and topical adverse effects
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R. Marsella and C. F. Nicklin

were noted. Some drug accumulation was observed at

the end of the treatment, but mean concentrations were
well below levels considered at increased risk for
toxicity.18,19 A commercial kit was used in this study for
the detection of tacrolimus concentrations, as it is
commercially available and widely reported in the
literature.3537 The range detected in the tacrolimus
treatment group was 0.1527.162 ng mL1. In this group,
there were two dogs with levels higher than 20 ng mL1
(levels considered at increased risk for toxicity in
humans and dogs). These values were detected after
4 weeks of treatment (at hours 2 and 4 in one dog and
at hour 6 in the other dog). Neither of these dogs showed
signs of toxicity or had any significant alteration in
their blood work. These dogs were not removed from
statistical analysis since the purpose of this investigation was to evaluate any systemic absorption. Despite
the levels in these two dogs, mean blood concentrations
were well below toxic levels. Finally, it is important to
note that the ELISA used in this pilot study measured
many tacrolimus metabolites, in addition to the whole
compound, so if these patients had any condition that
might have interfered with the metabolism of tacrolimus
the levels detected may have appeared elevated.
In conclusion, the results of this pilot study indicate
that a 0.3% tacrolimus lotion appears to be well tolerated in dogs and is moderately effective in decreasing
signs of AD. Larger, long-term studies are necessary to
further evaluate the therapeutic potential and toxicity
of topical tacrolimus in dogs.

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Rsum Cette tude a valu lefficacit dune lotion contenant 0.3% de tacrolimus (dose maximale de 0.3 mg kg1
par jour) pour le traitement de la dermatite atopique (AD). Labsorption systmique et les effets sur la numration
formule (CBC) et les constants biochimiques ont galement t tudis. Huit chiens ont t traits au hasard
soit par le tacrolimus soit par le vhicule. Les propritaires comme les investigateurs ne connaissaient pas le traitement administr. Aprs 4 semaines, une priode de 2 semaines sans traitement tait mise en place puis les groupes
taient inverss. Les propritaires devaient scorer le prurit toutes les semaines et les investigateurs scoraient
le prurit et lrythme au dbut et la fin de chaque priode de traitement. Les scores de prurit donns par les
investigateurs ont diminu significativement dans le groupe tacrolimus la fin de ltude (P = 0.03). Les scores
drythme donns par les investigateurs taient significativement plus faibles pour le groupe tacrolimus que pour
ceux du groupe placebo la fin de ltude (P = 0.005). Aucune difference na t note entre les groupes pour
lvaluation du prurit par le propritaire. Aucune modification des constantes hmatologiques ou biochimiques
na t observe. Les taux sanguins moyens de tacrolimus sont rests en dessous des niveaux toxiques.
Resumen Se evalu la eficacia de una locin de tacrolimus al 0.3% (dosis mxima: 0.3 mg kg1 al da) para el
tratamiento de la dermatitis atpica (AD). Tambin se investigaron la absorcin sistmica y sus efectos sobre los
recuentos celulares hematolgicos (CBC) y los paneles qumicos. Se asignaron ocho perros al azar a grupos de
tratamiento con una locin de tacrolimus o con un adyuvante. Tanto los propietarios como el investigador
desconocan el tratamiento. Despus de cuatro semanas, se estableci un periodo de 2 semanas de retirada del
producto, y se invirtieron los tratamientos. Los propietarios puntuaron el prurito semanalmente mientras el investigador puntu el prurito y el eritema al principio y al final de cada periodo de tratamiento. Las puntuaciones
del investigador sobre el prurito en el grupo del tacrolimus disminuyeron significativamente al final del estudio
(P = 0.03). Las puntuaciones del investigador sobre el eritema en el grupo del tacrolimus fueron significativamente inferiores que las del grupo placebo al final del estudio (P = 0.005). No exista diferencia entre los grupos
respecto a las puntuaciones sobre el prurito. No se observaron cambios en los paneles bioqumicos y hemticos.
Las concentraciones sanguneas medias de tacrolimus se encontraban por debajo de niveles txicos.
Zusammenfassung Die Wirksamkeit einer 0.3% Takrolimus-Lotion (maximale Dosis: 0.3 mg kg--1 pro Tag)
wurde in der Behandlung von atopischer Dermatitis (AD) bewertet. Die systemische Absorption und Wirkung
auf hmatologische und biochemische Parameter wurde ebenfalls untersucht. Acht Hunde wurden randomisiert
zwei Gruppen zugewiesen und entweder mit Takrolimus-Lotion oder nur mit dem Vehikel lokal behandelt. Die
Behandlung erfolgte doppelblind in Bezug auf Hundebesitzer und Untersucher. Nach 4 Behandlungswochen und
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210

R. Marsella and C. F. Nicklin

einer anschlieenden zweiwchigen Auswaschperiode wurden die Behandlungsregieme gewechselt. Die Besitzer
bewerteten den Grad des Juckreizes wchentlich, whrend der Untersucher den Grad des Juckreizes sowie des
Erythems jweils zu Beginn und am Ende jeder Behandlungsperiode bewertete. Die Werte des Untersuchers fr
den Grad des Juckreizes in der mit Takrolimus behandelten Gruppe wurden zum Ende der Studie signifikant
geringer (P = 0.03). Die Werte des Untersuchers fr den Grad des Erythems in der mit Takrolimus behandelten
Gruppe waren am Ende der Studie signifikant geringer als diejenigen in the Plazebogruppe (P = 0.005). Bezglich
der Bewertung des Juckreizes durch die Besitzer bestand kein Unterschied zwischen den Gruppen. Es wurden
keine Vernderungen hmatologischer oder biochemischer Parameter beobachtet. Die mittleren TakrolimusBlutkonzentrationen lagen unterhalb toxischer Werte.

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