Therapeutic index of H1-antihistamines: example of cetirizine

Rihoux, Jean‐Pierre

doi:10.1016/s1081-1206(10)62856-6

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…Plasma cetirizine concentrations from all formulations were higher than hydroxyzine concentrations because cetirizine is hydrophilic and has a much smaller apparent volume of distribution. 28 The hydroxyzine concentrations obtained after GB, when plotted versus time as shown in Figure 2, are similar to those that would be obtained after oral dosing, with a maximum concentration at 1 hour, followed by decreasing concentrations as the hydroxyzine was eliminated. 21 This result may be due to the hydroxyzine being released rapidly from the GB and absorbed quickly thorough the skin as a bolus dose.…”

Section: Discussionsupporting

confidence: 69%

Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

Elzainy

Simons

et al. 2003

AAPS PharmSci

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Hydroxyzine, an effective but sedating H1-antihistamine is given orally to treat allergic skin disorders. This study was performed to assess the peripheral H(1)-antihistaminic activity and extent of systemic absorption of hydroxyzine from liposomes applied to the skin. Using L-alpha-phosphatidylcholine (PC), small unilamellar vesicles (SUVs) and multilamellar vesicles (MLVs) containing hydroxyzine were prepared. Hydroxyzine in Glaxal Base (GB) was used as the control. Using a randomized, crossover design, each formulation, containing 10 mg of hydroxyzine, was applied to the shaved backs of 6 rabbits (3.08 +/- 0.05 kg). Histamine-induced wheal tests and blood sampling were performed at designated time intervals up to 24 hours. Compared with baseline, hydroxyzine from all formulations significantly suppressed histamine-induced wheal formation by 75% to 95% for up to 24 hours. Mean maximum suppression, 85% to 94%, occurred from 2 to 6 hours, with no differences among the formulations. The areas of plasma hydroxyzine concentration versus time area under the curve (AUCs) from PC-SUV and PC-MLV, 80.1 +/- 20.8 and 78.4 +/- 33.9 ng/mL/h, respectively, were lower than that from GB, 492 +/- 141 ng/mL/h (P < or =.05) over 24 hours. Plasma concentrations of cetirizine arising in-vivo as the active metabolite of hydroxyzine, from PC-SUV, PC-MLV, and GB, were similar with AUCs of 765 +/- 50, 1035 +/- 202, and 957 +/- 227 ng/mL/h, respectively (P < or =.05). Only 0.02% to 0.06% of the initial hydroxyzine dose remained on the skin after 24 hours. In this model, hydroxyzine from SUV and MLV had excellent topical H1-antihistaminic activity, and minimal systemic exposure occurred. Cetirizine formed in-vivo contributed to some of H1-antihistaminic activity.

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Section: Discussionsupporting

confidence: 69%

Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

Elzainy

Simons

et al. 2003

AAPS PharmSci

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“…In addition to the greater potency of Ioratadine over astemizole, 12 its prompt action, and lack of accumulation even with long-term use, 11 we were also aware of a few reports of rare side effects when using other antihistamine drugs other than Ioratadine. 13,14 There are only anecdotal reports on the use of antihistamines for vascular headaches. 15 Controlled trials have failed to prove any benefit of such prophylactic use either for vascular headaches 16 or cluster headache.…”

Section: Commentsmentioning

confidence: 99%

Antihistamine Responsive Cluster Headache in a Teenaged Girl

1997

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Episodic cluster headache is a well-recognized entity usually starting in the second decade of life. Uncommonly, the first typical symptoms may present in the first decade of life, but are rarely recognized as such during childhood. We report a 12-year-old girl who presented with a 1-year history of bouts of right-sided hemicrania with ipsilateral, clearly demarcated, redness and itching of the skin of the face, lasting from 15 minutes to 2 hours per day. The episodes recurred up to several times daily for a few days and were followed by remissions lasting up to 2 months. Thorough investigations failed to prove any definite cause. Antihistamine prophylaxis, first with astemizole and then with Ioratadine, proved to be very effective. During the follow-up period of more than 3 years, such a prophylactic regimen provided excellent relief, with only two relapses due to noncompliance. We suggest that in a sequential treatment trial for cluster headache during childhood, antihestamines should have their place, especially in those cases where clinical evidence may suggest histamine involvement.Key words: cluster headache, childhood, Ioratadine prophylaxis, urinary methylhistamine (Headache 1997;37:296-298) Episodic cluster headache is defined as a severe unilateral head or facial pain, which lasts from 15 minutes to 3 hours and is commonly associated with conjunctival injection, lacrimation, and nostril blockage on the same side. Attacks can occur once or several times daily for a period of weeks or months. 1 Attacks with the same characteristics but of briefer duration and recurring more frequently (up to 30 times) during the day were named chronic paroxysmal hemicrania (CPH) by Sjaastad and Dale in 19762 and were reported to respond well to indomethacin. Also an episodic form was recognized with very frequent daily attacks lasting for a few weeks followed by a long symptom-free period with relapses only after months or even years. 3 To avoid different terminology for all these forms, the term "cluster headache syndrome" was proposed. 4 The pathophysiology of cluster headache is still unclear. Histamine-induced attacks in susceptible individuals were recognized in 1941 by Horton 5 whose name is sometimes used as an eponym for this type of headache. Some authors have detected high levels of histamine in blood during the attacks, 6,7 but treatment with antihistamine drugs was usually described as useless in such cases. 8 CASE HISTORYA 12-year-old girl was referred to our outpatient department with possible trigeminal neuralgia. Detailed history revealed that she had been suffering for more than a year from occasional paroxysmal attacks of right-sided hemicrania associated with ipsilateral itching of facial skin and clearly demarcated areas of purple-redness. These attacks usually lasted for 15 minutes, but were occasionally prolonged up to 2 hours and resolved spontaneously. Up to four attacks could occur in a day in a cluster manner. Remissions between the attacks were of variable duration, not exceeding 3 months. N...

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“…The somnolence that sometimes occurs after oral administration is dose dependent, and generally mild. 6 Liposomes, which are closed vesicles of phospholipid bilayers or lamellae with enclosed aqueous layers and cores, are able to encapsulate hydrophobic and hydrophilic ingredients into their structure. 7 The degree of saturation of the free fatty acid chains in phospholipids (PL), the principle ingredient of liposome formulations, affects the transition temperature (Tc) of the PL.…”

Section: Introductionmentioning

confidence: 99%

Cetirizine from topical phosphatidylcholine-hydrogenated liposomes: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

Elzainy

Simons

et al. 2004

AAPS J

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Cetirizine, an effective, minimally sedating, second-generation H1-antihistamine is widely used orally to treat allergic skin disorders. This study was performed to assess the peripheral H1-antihistaminic activity and extent of systemic absorption of cetirizine from liposomes applied to the skin. Cetirizine was incorporated into small unilamellar vesicles (SUV) and multilamellar vesicles (MLV) prepared using L-alpha-phosphatidylcholine hydrogenated (HPC), and into Glaxal Base (GB) as the control. In a randomized, crossover study, each formulation, containing 10 mg of cetirizine, was applied to the depilated backs of 6 rabbits (3.08 +/- 0.05 kg). Histamine-induced wheal tests and blood sampling were performed before cetirizine application and at designated times for up to 24 hours afterwards. Compared with baseline, histamine-induced wheal formation was suppressed by cetirizine in SUV only at 24 hours, in MLV from 0.5 to 24 hours, and in GB from 0.5 to 8 hours (P < or = .05). Wheal suppression by cetirizine in SUV at 24 hours (91.7% +/- 5.2%) and in MLV from 1 to 24 hours (93.8% +/- 2.2% to 76.2% +/- 6.5%) was greater than in GB (36.5% +/- 7.4% to 60.6% +/- 14.2%) from 1 to 24 hours (P < or = .05). Faster onset, as well as greater and more persistent suppression was obtained from cetirizine in MLV. Plasma cetirizine concentrations from MLV (area under the curve [AUC] of 221.2 +/- 42.3 ng x hr/mL) were lower than from GB (AUC of 248.3 +/- 34.6 ng.hr/mL). In this model, cetirizine from MLV had excellent topical H(1)-antihistamine activity, while systemic exposure was reduced, compared with cetirizine from GB.

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Therapeutic index of H1-antihistamines: example of cetirizine

Cited by 4 publications

References 21 publications

Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

Hydroxyzine from topical phospholipid liposomal formulations: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

Antihistamine Responsive Cluster Headache in a Teenaged Girl

Cetirizine from topical phosphatidylcholine-hydrogenated liposomes: Evaluation of peripheral antihistaminic activity and systemic absorption in a rabbit model

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