Journal of Dermatological Treatment, 2013; 24: 473–476

© 2013 Informa Healthcare USA on behalf of Informa UK Ltd.

ISSN: 0954-6634 print / 1471-1753 online
DOI: 10.3109/09546634.2013.777152

ORIGINAL ARTICLE

Comparison of effects of 5 and 10 mg oral desloratadine and

levocetirizine on histamine-induced wheal and flare response in
healthy volunteers
Songül Bulca1, Dilek Bayramgürler2, Evren Odyakmaz Demirsoy2, Melike Yavuz3, Aysun Ş ikar Aktürk2,
Nilgün Bilen2 & Rebiay Kıran2
1
Düzce Public Hospital, Düzce, Turkey, 2Department of Dermatology, Kocaeli University Medical Faculty, Kocaeli, Turkey and
3
Department of Public Health, Kocaeli University Medical Faculty, Kocaeli, Turkey

Background: Levocetirizine and desloratadine are mostly used as
H1-antihistamines in the treatment of allergic disease in 5 and
10 mg doses. Objective: In this study, the efficacy of single oral
dosages of 5 and 10 mg desloratadine and levocetirizine were
compared by using histamine-induced wheal and flare reactions.
Methods: Eighty healthy volunteers were randomized for four
double-blinded treatment with desloratadine 5 and 10 mg and
levocetirizine 5 and 10 mg. Wheal and flare responses were
produced by histamine. Measurements were performed just
before the ingestion of antihistamines (baseline) and
afterward at 30, 60, 240 min and 24 h. The values obtained
for each antihistamine were compared with baseline values.
Results: It was found that except the flare reactions at 30th
min, levocetirizine 5 and 10 mg suppressed histamine-
induced wheal and flare reactions more than desloratadine
5 and 10 mg did. There were not any significant differences
between desloratadine 5 and 10 mg in all periods. Levocetirizine
10 mg suppressed wheal and flare reactions significantly more
than levocetirizine 5 mg only at 24th h. Conclusion: In this study,
it was observed that levocetirizine 5 and 10 mg had a higher
activity than desloratadine 5 and 10 mg.
Key words: desloratadine, levocetirizine, histamine prick test, wheal
response, flare response
Introduction
Antihistamines suppress histamine-related symptoms by their
reversible and competitive effects on H1 receptors and these drugs
are accepted as the first-line treatment agents in the field of allergic
diseases (1). Among non-sedating antihistamines, cetirizine and
loratadine have been used for many years and their effects on the
skin have been compared quantitatively via evaluation of histamine-
induced wheal and flare reactions (2–4). In the recent years,
levocetirizine (L) and desloratadine (D) which are derived from
cetirizine and loratadine, respectively are more commonly used in
treatment of diseases associated with histamine release. It is notified
in drug information leaflets that both L5 mg/day and D5 mg/day
are sufficient to control symptoms induced by histamine. But in
practice it is commonly encountered that these drugs cannot
alleviate the symptoms in most of chronic idiopathic urticaria
patients when used at conventionally prescribed dosages (5). In
this situation although it is recommended that an increase in the
antihistamine doses up to fourfold in patients not responding to the
conventional doses before considering an alternative treatment (6),
there is only one well-designed, randomized controlled study
comparing the efficacy of antihistamines in higher doses to date (7).
In this background, the authors decided to evaluate and
compare the efficacy of 5 and 10 mg D and L that are the
most commonly used non-sedative antihistamines in chronic
urticaria in their country.
Methods
This double-blinded, single dose, cross-over study was performed
with 80 healthy volunteers after ethical approval was obtained.
Forty male and 40 female adults aged 18–45 years (mean
23.6 years) were included in the study.
Subjects who had any acute or chronic illness, had taken H1 or
H2 receptor antagonist, systemic corticosteroid, mast cell stabi-
lizer or tricyclic antidepressant drug within the previous month,
or had a history of idiosyncratic reaction to histamine or anti-
histamines were excluded. Also pregnant and lactating women
were excluded. The study population was divided into four
groups, each group comprising 10 female and 10 male volunteers.
Volunteers in group 1 received a single 5 mg oral dose of D
(Aerius
, Novartis), volunteers in group 2 received a single 10 mg
oral dose of D, volunteers in group 3 received a single 5 mg oral
dose of L (Xyzal
, UCB Pharma) and volunteers in group
4 received a single 10 mg oral dose of L.
The study was performed during a 3-day period. The wheal
and flare responses were produced by the first investigator and the
baseline values were determined on the first day. On the second
day, the medications were administered by the second investigator
with a glass of water 2 h after breakfast. Afterward the wheal and
flare responses were measured at 30, 60, 240 min after drug
ingestion, by the first investigator. On day 3, 24 h after antihis-
tamine ingestion, wheal and flare responses were measured again
by the first investigator. The first investigator had no knowledge
about the drugs at any stage of the investigation. After skin tests,
subjects were questioned about adverse effects such as sedation,
disorientation, dizziness, drowsiness, dry mouth, visual changes,
nausea, vomiting and diarrhea.

Correspondence: Evren Odyakmaz Demirsoy, Department of Dermatology, Kocaeli University Medical Faculty, Kocaeli, Turkey. Tel: +02623037262.
E-mail: evrenodyakmaz@yahoo.com
(Received 24 December 2012; accepted 16 January 2013)
 S. Bulca et al.

Table I. Mean wheal and flare responses (mm ± SEM) at baseline and after antihistamine ingestion.
Group n Baseline 30 min 60 min 240 min 24 h
Wheal
D5 mg 20 6.80 ± 1.60 6.35 ± 1.54 6.95 ± 2.01 4.88 ± 1.09 4.53 ± 1.22
D10 mg 20 6.40 ± 1.79 6.10 ± 1.25 6.20 ± 1.20 4.60 ± 1.23 4.43 ± 0.92
L5 mg 20 6.40 ± 1.85 6.15 ± 1.86 4.80 ± 1.51 2.05 ± 1.23 .28 ± 1.11
L10 mg 20 5.95 ± 1.12 5.28 ± 1.96 4.28 ± 1.76 1.58 ± 0.59 1.93 ± 0.56
Flare
D5 mg 20 36.08 ± 11.64 38.68 ± 11.12 37.75 ± 12.81 28.23 ± 10.97 23.35 ± 12.26
D10 mg 20 30.35 ± 10.22 28.75 ± 9.36 30.15 ± 9.11 19.10 ± 8.26 14.82 ± 8.06
L5 mg 20 35.28 ± 8.81 36.35 ± 12.11 26.38 ± 9.13 7.15 ± 3.97 11.73 ± 6.68
L10 mg 20 35.75 ± 10.80 31.70 ± 11.31 26.28 ± 11.33 6.08 ± 1.47 6.83 ± 2.64

Assessment of epicutaneous tests
Prick test with 1% histamine solution (ALK-Abelló Lab, Madrid/
Spain) was used to induce the wheal and flare responses on the
volar aspect of the forearms. After 10 min, wheal and flare areas
were assessed by measuring the largest diameter and its perpen-
dicular diameter to quantify the skin responses. The wheal and
flare responses were determined by calculating the mean of these
two values.
The values obtained for each dosage of antihistamines at 0, 30,
60, 240 min and 24 h were compared with the baseline values and
“% suppression ratio” was calculated (% suppression ratio =
(wheal/flare areabaseline - wheal/flare areatime t)/(wheal/flare
areabaseline)  100) for each group for all time periods and
subsequently compared with each other.
Statistical analysis
Results were expressed as the means ± SEM. Statistical signifi-
cance of differences between groups was determined by Kruskal–
Wallis test followed by Mann–Whitney U test when appropriate;
p < 0.05 was taken to indicate statistical significance.
Results
There was no significant difference among the study groups in
terms of age, sex and weight. At baseline there was no significant
difference among the four groups in mean wheal and flare
responses. Mean wheal and flare responses at baseline and after
antihistamine ingestion are shown in Table I.
Percentage inhibition of wheal and flare responses by test drugs
is shown in Figures 1 and 2.
There were not any significant differences between D5 mg and
D10 mg in all periods for the suppression of the both wheal and
flare responses. Except the results obtained at 30 min, L5 and
L10 more significantly suppressed the wheal and flare responses
than D5.
When L5 mg compared with L10 mg, it was observed that
although L10 mg had higher activity on wheal and flare response
than L5 mg in all times, it was statistically significant only at 24 h.
L5 mg suppressed the mean wheal and flare response significantly
more than D10 mg in all times.
Sedation was the only side effect reported by the patients.
There was no statistically significant difference between the
groups in terms of sedation.
Discussion
In the present study, it was found that, except the flare reactions
calculated at 30th min, both L5 mg and L10 mg suppressed
histamine-induced wheal and flare reactions more effectively than
D5 mg and D10 mg. Previous studies with 5 mg doses of each
drug have shown that L had a superior activity than D in
inhibition of the wheal and flare response to histamine (8–11).
Popov et al. gave single doses of 1.25, 2.5, 5 mg L, 2, 2.5, 10 mg D
and placebo to 24 healthy male non-atopic volunteers at weekly
intervals. They found that all doses of L reduced the wheal
diameter more than placebo whereas only 10 mg of D had a

100

80

60
Desloratadine 5 mg

40 Desloratadine 10 mg
Levocetirizine 5 mg

20 Levocetirizine 10 mg

00

–20
30 min 60 min 240 min 24 h

Figure 1. Percentage inhibition of flare responses to the antihistamines.


80
60
40
20
00
–20
30 min 60 min 240 min
Figure 2. Percentage inhibition of wheal responses to the antihistamines.
significantly superior activity than placebo. Reducing effect of
L1.25 mg was more prominent than D10 mg. It was also shown
that in contrast to D the inhibition of wheal and flare reaction for
L was dose dependent. Statistically significant difference was not
observed between these two drugs with respect to the degree of
sedation or motricity test (8).
Similar to Popov et al., the authors found no statistical
significant difference in D5 mg and D10 mg in inhibition of
wheal and flare reactions. On the other hand, they revealed that
L10 mg reduced these responses more than L5 mg at only 24 h. In
another study reported by Purohit et al., D5 mg, L5 mg and
placebo were compared with each other on 18 healthy volunteers
using histamine-induced wheal and flare responses. It was found
that L5 mg was more efficacious than D5 mg on histamine-
induced wheal and flare response at 24 h (11).
Dhanya et al. compared the effects of L5 mg, D5 mg and
fexofenadine 180 mg on histamine-induced wheal and flare
responses. They observed fexofenadine 180 mg showed a statisti-
cally significant suppression of wheal size compared with L5 mg and
D5 mg at 30 min. Two and three hours after administration, wheal
suppression was less with D5 mg than L5 mg and fexofenadine (10).
The main cause of difference between effectiveness of L and D
on histamine-induced wheal and flare responses might be related
with pharmacological properties of these agents such as
H1 receptor affinity, distribution volume in human body, extra-
cellular concentration and binding rate to plasma proteins (12,13).
Gillard et al. calculated the receptor affinity 4 h after oral ingestion
of D and L and found it as 70% for D and 90% for L (13), whereas
D had a longer half-life and H1 receptor binding time than L
(12,13). The other predicting factor of the effect of a drug is
plasma distribution volume (14). If a drug has a high plasma
distribution volume it will have a weak effect. It was observed that
L had a lower plasma distribution volume than D (15). All of these
pharmacokinetic properties may explain superiority of L over D in
wheal and flare response to histamine. If a single standard and
high dose of these agents were considered D might have a weak
activity, but when they are used for a long time period as in
chronic allergic diseases it should be taken into account that D has
a longer half-life and receptor binding time than L (9).
In overall comparison in experimental studies evaluating the
effectiveness of D and L on histamine-induced wheal and flare
response, it was found that L5 mg had a higher activity than
D5 mg (8–10). The authors observed L5 mg and L10 mg had a
Levocetirizine, desloratadine and wheal and flare response 
Desloratadine 5 mg
Desloratadine 10 mg
Levocetirizine 5 mg
Levocetirizine 10 mg
24 h
higher activity than D5 mg and D10 mg. But in clinical practice,
the efficacy of these drugs in patients who have to use them for
long time periods is still not clear. The number of studies on this
subject evaluating the real patients with allergic symptoms is
limited in dermatology literature. In one of these studies, L5 mg
daily was compared with D5 mg daily in 886 chronic idiopathic
urticaria patients and it was found that L decreased pruritus
severity, pruritus duration, size of wheals and chronic idiopathic
urticaria composite score both after the first week and at the end
of treatment more than D. There were no differences between two
groups in terms of adverse effect (16). The clinical result derived
from this study is consistent with the results obtained from the
experimental studies (8,9,11).
The authors also compared D10 mg and L10 mg in daily
practice. They found that both L5 mg and L10 mg decreased
histamine-induced wheal and flare response more than D10 mg.
In a clinical study comprising 80 tertiary referral patients with
chronic, difficult-to-treat urticaria conducted by Staevska et al., D
and L were compared at conventional doses and when needed at
doses of up to fourfold. According to this study, only nearly 16%
of patients became symptom-free at the conventional daily doses.
It was shown that non-responsive patients to D became symptom-
free with same high doses of L in remaining patients whose doses
were increased up to fourfold whereas switch to D had no benefit
in any of their patients who were not symptom-free on L (7).
Conclusion
Histamine-induced wheal and flare response is a reliable and
commonly used method investigating the effects of antihista-
mines, but also these studies should be supported with large
clinical trials giving more valuable results.
Declaration of interest: The authors report no conflicts of
interest. The authors alone are responsible for the content and
writing of the paper.
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