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bulca2013 (ส่งพี่)
ORIGINAL ARTICLE
1
Dzce Public Hospital, Dzce, 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 patients when used at conventionally prescribed dosages (5). In
H1-antihistamines in the treatment of allergic disease in 5 and this situation although it is recommended that an increase in the
10 mg doses. Objective: In this study, the efcacy of single oral antihistamine doses up to fourfold in patients not responding to the
dosages of 5 and 10 mg desloratadine and levocetirizine were conventional doses before considering an alternative treatment (6),
compared by using histamine-induced wheal and are reactions. there is only one well-designed, randomized controlled study
Methods: Eighty healthy volunteers were randomized for four comparing the efcacy of antihistamines in higher doses to date (7).
double-blinded treatment with desloratadine 5 and 10 mg and In this background, the authors decided to evaluate and
levocetirizine 5 and 10 mg. Wheal and are responses were compare the efcacy of 5 and 10 mg D and L that are the
produced by histamine. Measurements were performed just most commonly used non-sedative antihistamines in chronic
before the ingestion of antihistamines (baseline) and urticaria in their country.
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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 are 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
J Dermatolog Treat Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 03/27/15
Assessment of epicutaneous tests Percentage inhibition of wheal and are responses by test drugs
Prick test with 1% histamine solution (ALK-Abell Lab, Madrid/ is shown in Figures 1 and 2.
Spain) was used to induce the wheal and are responses on the There were not any signicant differences between D5 mg and
volar aspect of the forearms. After 10 min, wheal and are areas D10 mg in all periods for the suppression of the both wheal and
were assessed by measuring the largest diameter and its perpen- are responses. Except the results obtained at 30 min, L5 and
dicular diameter to quantify the skin responses. The wheal and L10 more signicantly suppressed the wheal and are responses
are responses were determined by calculating the mean of these than D5.
two values. When L5 mg compared with L10 mg, it was observed that
The values obtained for each dosage of antihistamines at 0, 30, although L10 mg had higher activity on wheal and are response
60, 240 min and 24 h were compared with the baseline values and than L5 mg in all times, it was statistically signicant only at 24 h.
% suppression ratio was calculated (% suppression ratio = L5 mg suppressed the mean wheal and are response signicantly
(wheal/are areabaseline - wheal/are areatime t)/(wheal/are more than D10 mg in all times.
areabaseline) 100) for each group for all time periods and Sedation was the only side effect reported by the patients.
subsequently compared with each other. There was no statistically signicant difference between the
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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
80
60
Desloratadine 5 mg
40 Desloratadine 10 mg
Levocetirizine 5 mg
20 Levocetirizine 10 mg
00
J Dermatolog Treat Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 03/27/15
20
30 min 60 min 240 min 24 h
signicantly superior activity than placebo. Reducing effect of higher activity than D5 mg and D10 mg. But in clinical practice,
L1.25 mg was more prominent than D10 mg. It was also shown the efcacy of these drugs in patients who have to use them for
that in contrast to D the inhibition of wheal and are reaction for long time periods is still not clear. The number of studies on this
L was dose dependent. Statistically signicant difference was not subject evaluating the real patients with allergic symptoms is
observed between these two drugs with respect to the degree of limited in dermatology literature. In one of these studies, L5 mg
sedation or motricity test (8). daily was compared with D5 mg daily in 886 chronic idiopathic
Similar to Popov et al., the authors found no statistical urticaria patients and it was found that L decreased pruritus
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signicant difference in D5 mg and D10 mg in inhibition of severity, pruritus duration, size of wheals and chronic idiopathic
wheal and are reactions. On the other hand, they revealed that urticaria composite score both after the rst week and at the end
L10 mg reduced these responses more than L5 mg at only 24 h. In of treatment more than D. There were no differences between two
another study reported by Purohit et al., D5 mg, L5 mg and groups in terms of adverse effect (16). The clinical result derived
placebo were compared with each other on 18 healthy volunteers from this study is consistent with the results obtained from the
using histamine-induced wheal and are responses. It was found experimental studies (8,9,11).
that L5 mg was more efcacious than D5 mg on histamine- The authors also compared D10 mg and L10 mg in daily
induced wheal and are response at 24 h (11). practice. They found that both L5 mg and L10 mg decreased
Dhanya et al. compared the effects of L5 mg, D5 mg and histamine-induced wheal and are response more than D10 mg.
fexofenadine 180 mg on histamine-induced wheal and are In a clinical study comprising 80 tertiary referral patients with
responses. They observed fexofenadine 180 mg showed a statisti- chronic, difcult-to-treat urticaria conducted by Staevska et al., D
cally signicant suppression of wheal size compared with L5 mg and and L were compared at conventional doses and when needed at
D5 mg at 30 min. Two and three hours after administration, wheal doses of up to fourfold. According to this study, only nearly 16%
suppression was less with D5 mg than L5 mg and fexofenadine (10). of patients became symptom-free at the conventional daily doses.
The main cause of difference between effectiveness of L and D It was shown that non-responsive patients to D became symptom-
on histamine-induced wheal and are responses might be related free with same high doses of L in remaining patients whose doses
with pharmacological properties of these agents such as were increased up to fourfold whereas switch to D had no benet
H1 receptor afnity, distribution volume in human body, extra- in any of their patients who were not symptom-free on L (7).
cellular concentration and binding rate to plasma proteins (12,13).
Gillard et al. calculated the receptor afnity 4 h after oral ingestion
Conclusion
of D and L and found it as 70% for D and 90% for L (13), whereas Histamine-induced wheal and are response is a reliable and
D had a longer half-life and H1 receptor binding time than L commonly used method investigating the effects of antihista-
(12,13). The other predicting factor of the effect of a drug is mines, but also these studies should be supported with large
plasma distribution volume (14). If a drug has a high plasma clinical trials giving more valuable results.
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 Declaration of interest: The authors report no conicts of
pharmacokinetic properties may explain superiority of L over D in interest. The authors alone are responsible for the content and
wheal and are response to histamine. If a single standard and writing of the paper.
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 References
chronic allergic diseases it should be taken into account that D has 1. ODonoghue M, Tharp MD. Antihistamines and their role as anti-
a longer half-life and receptor binding time than L (9). pruritics. Dermatol Ther. 2005;18:333340.
In overall comparison in experimental studies evaluating the 2. Simons FE, McMillan JL, Simons KJ. A double-blind, single-dose,
crossover comparison of cetirizine, terfenadine, loratadine, astemizole,
effectiveness of D and L on histamine-induced wheal and are and chlorpheniramine versus placebo: suppressive effects on
response, it was found that L5 mg had a higher activity than histamine-induced wheals and ares during 24 hours in normal
D5 mg (810). The authors observed L5 mg and L10 mg had a subjects. J Allergy Clin Immunol. 1990;86:540547.
S. Bulca et al.
3. Kontou-Fili K, Paleologos G, Herakleous M. Suppression of 10. Dhanya NB, Thasleem Z, Rai R, Srinivas CR. Comparative efcacy of
histamine-induced skin reactions by loratadine and cetirizine diHCl. levocetirizine, desloratidine and fexofenadine by histamine wheal
Eur J Clin Pharmacol. 1989;36:617619. suppression test. Indian J Dermatol Venereol Leprol. 2008;74:361363.
4. Bayramgurler D, Bilen N, Apaydyn R, Altintas L, Sal G, 11. Purohit A, Melac M, Pauli G, Frossard N. Twenty-four-hour activity
Dokmeci S, et al. Effects of acrivastine, loratadine and cetirizine on and consistency of activity of levocetirizine and desloratadine in the
histamine-induced wheal and are responses. Clin Exp Dermatol. skin. Br J Clin Pharmacol. 2003;56:388394.
1999;24:407411. 12. Gillard M, Van Der Perren C, Moguilevsky N, Massingham R,
5. DuBuske L. Desloratadine for chronic idiopathic urticaria: a review of Chatelain P. Binding characteristics of cetirizine and levocetirizine
clinical efcacy. Am J Clin Dermatol. 2007;8:271283. to human H(1) histamine receptors: contribution of Lys(191) and Thr
6. Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, (194). Mol Pharmacol. 2002;61:391399.
Church MK, Gimenez-Arnau AM, et al. EAACI/GA(2)LEN/EDF/ 13. Gillard M, Christophe B, Wels B, Peck M, Massingham R,
WAO guideline: management of urticaria. Allergy. 2009;64:14271443. Chatelain P. H1 antagonists: receptor afnity versus selectivity.
7. Staevska M, Popov TA, Kralimarkova T, Lazarova C, Kraeva S, Inamm Res. 2003;52:S49S50.
Popova D, et al. The effectiveness of levocetirizine and desloratadine 14. Harvey RA, Champe PC, Mycek MJ, Gertner SB,
in up to 4 times conventional doses in difcult-to-treat urticaria. Perper MM. Lippincotts illustrated reviews: pharmacology. Philadel-
J Allergy Clin Immunol. 2010;125:676682. phia: J.B. Lippincott Co, 1992.
8. Popov TA, Dumitrascu D, Bachvarova A, Bocsan C, Dimitrov V, 15. Molimard M, Diquet B, Benedetti MS. Comparison of pharmacoki-
J Dermatolog Treat Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 03/27/15
Church MK. A comparison of levocetirizine and desloratadine in the netics and metabolism of desloratadine, fexofenadine, levocetirizine
histamine-induced wheal and are response in human skin in vivo. and mizolastine in humans. Fundam Clin Pharmacol. 2004;18:
Inamm Res. 2006;55:241244. 399411.
9. Denham KJ, Boutsiouki P, Clough GF, Church MK. Comparison of the 16. Potter PC, Kapp A, Maurer M, Guillet G, Jian AM, Hauptmann P, et al.
effects of desloratadine and levocetirizine on histamine-induced wheal, Comparison of the efcacy of levocetirizine 5 mg and desloratadine
are and itch in human skin. Inamm Res. 2003;52:424427. 5 mg in chronic idiopathic urticaria patients. Allergy. 2009;64:596604.
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