Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers

Russell, Tanya L.; Stoltz, M.; Weir, Scott J.

doi:10.1016/s0009-9236(98)90052-2

Cited by 108 publications

(90 citation statements)

References 10 publications

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“…First, it must be absorbed into the systemic circulation after oral dosage with a tablet or capsule. Most H 1 -antihistamines are well absorbed, the exception being fexofenadine, which has a very variable absorption because of the influence of active transporting proteins as described later[29,30]. Second is the extent of plasma binding which, with H 1 -antihistamines, is high, varying from ~65% with desloratadine to ~90% for levocetirizine[31].…”

Section: Second-generation H1-antihistaminesmentioning

confidence: 99%

Pharmacology of Antihistamines

Church¹,

Church²

2011

World Allergy Organization Journal

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This article reviews the molecular biology of the interaction of histamine with its H1-receptor and describes the concept that H1-antihistamines are not receptor antagonists but are inverse agonists i.e. they produce the opposite effect on the receptor to histamine. It then discourages the use of first-generation H1-antihistamines in clinical practice today for two main reasons. First, they are less effective than second generation H1-antihistamines. Second, they have unwanted side effects, particularly central nervous system and anti-cholinergic effects, and have the potential for causing severe toxic reactions which are not shared by second-generation H1-antihistamines. There are many efficacious and safe second-generation H1-antihistamines on the market for the treatment of allergic disease. Of the three drugs highlighted in this review, levocetirizine and fexofenadine are the most efficacious in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals while fexofenadine has a relatively short duration of action requiring twice daily administration for full all round daily protection. While desloratadine is less efficacious, it has the advantages of rarely causing somnolence and having a long duration of action. Lastly, all H1-antihistamines have anti-inflammatory effects but it requires regular daily dosing rather than dosing 'on-demand' for this effect to be clinically demonstrable.

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Section: Second-generation H1-antihistaminesmentioning

confidence: 99%

Pharmacology of Antihistamines

Church¹,

Church²

2011

World Allergy Organization Journal

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“…Não atravessa a BHE, é minimamente metabolizada e suas propriedades farmacocinéticas permitem que seja utilizada em dose única diá-ria 5,40,41 .…”

Section: Fexofenadinaunclassified

“…As evidências indicam que a FEX é segura e bem tolerada [44][45][46][47]50 , mesmo em doses até 11 vezes maiores do que as terapêuticas 40 . É destituída de efeitos anticolinérgicos clinicamente significativos 51 .…”

Section: Fexofenadinaunclassified

New antihistamines: a critical view

Camelo-Nunes¹

2006

J Pediatr (Rio J)

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Objective: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders.Sources: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines.Summary of the findings: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit antiinflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. Conclusions:On the basis of the evidence on H1 antihistamines, none of them deserve the title third-generation antihistamine. As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS. J Pediatr (Rio J). 2006;82(5 Suppl):S173-80: Antihistamines, desloratadine, fexofenadine, levocetirizine, rupatadine. ResumoObjetivo: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas.Fontes dos dados: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos.

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“…It does not cross the BBB, is minimally metabolized and its pharmacokinetic properties allow it to be taken in a single daily dose. 5,40,41 In models constructed to evaluate its action in skin, FEX revealed a potent suppressive effect over histamineinduced wheal and flare. 9,10,42 In patients with AR subjected to nasal challenge it promoted significant improvement in nasal flow and symptom score, when compared with a placebo.…”

Section: More Recent Antihistaminesmentioning

confidence: 99%

“…49 Evidence indicates that FEX is safe and well-tolerated, [44][45][46][47]50 even at doses up to 11 times the therapeutic dose. 40 It is devoid of clinically significant anticholinergic effects. 51 No other H1 antihistamine has been studied as much as FEX to investigate potential cardiotoxic effects.…”

Section: More Recent Antihistaminesmentioning

confidence: 99%

Novos anti-histamínicos: uma visão crítica

Camelo-Nunes¹

2006

J. Pediatr. (Rio J.)

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Objective: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders.Sources: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines.Summary of the findings: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals.Conclusions: On the basis of the evidence on H1 antihistamines, none of them deserve the title third-generation antihistamine. As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS. J Pediatr (Rio J). 2006;82(5 Suppl):S173-80: Antihistamines, desloratadine, fexofenadine, levocetirizine, rupatadine.

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Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers

Abstract: Fexofenadine hydrochloride was well tolerated at oral doses up to 11 times the recommended therapeutic dose. In addition, fexofenadine hydrochloride showed significant antihistaminic activity and dose-proportional pharmacokinetics over a wide dosing range.

Cited by 108 publications

References 10 publications

Pharmacology of Antihistamines

Pharmacology of Antihistamines

New antihistamines: a critical view

Novos anti-histamínicos: uma visão crítica

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