Topical Iontophoretic Administration of Acyclovir for the Episodic Treatment of Herpes Labialis: A Randomized, Double-Blind, Placebo-Controlled, Clinic-Initiated Trial

Morrel, Eric M.; Spruance, Spotswood L.; Goldberg, Dennis I.

doi:10.1086/505872

Cited by 31 publications

(19 citation statements)

References 23 publications

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“…This may be due in part to the timing of viral replication and treatment initiation. Since viral replication is rapidly controlled (1 to 2 days) by host immune responses (8), if the antiviral drug is applied after viral replication reaches its maximum, there is little opportunity for the drug to have a significant effect, as demonstrated by the differences in efficacy observed when antivirals are initiated early (during the prodrome or erythema stages) versus late (during the vesicle or later stages) (14)(15)(16)(17)(18).…”

Section: Dual Disease Processes In Herpes Simplex Labialis Recurrencesmentioning

confidence: 99%

Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis

Hull

Levin

Tyring³

et al. 2014

Antimicrob Agents Chemother

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c Historically, the primary target for research and treatment of recurrent herpes simplex labialis (HSL) has been limited to inhibiting herpes simplex virus (HSV) replication. Antiviral monotherapy, however, has proven only marginally effective in curtailing the duration and severity of recurrent lesions. Recently, the role of inflammation in the progression and resolution of recurrences has been identified as an additional target. This was evaluated in a randomized study comparing combination topical 5% acyclovir-1% hydrocortisone cream (AHC) with 5% acyclovir alone (AC; in the AHC vehicle) and the vehicle. The efficacy of each topical therapy was evaluated for cumulative lesion size-a novel composite efficacy endpoint incorporating episode duration, lesion area, and proportion of nonulcerative lesions. In that study, cumulative lesion area was significantly decreased with AHC compared with AC (25% decrease; P < 0.05) and the vehicle (50% decrease; P < 0.0001). As research continues in this arena, cumulative lesion area should be included as a measure of efficacy in clinical trials of recurrent HSL therapies.T he seroprevalence of herpes simplex virus 1 (HSV-1), the HSV type most often associated with herpes simplex labialis (HSL) or cold sores, is estimated to be 58% among immunocompetent Americans 14 to 49 years of age (1) and 31% among children 6 to 13 years of age (2). Approximately 15 to 40% of these seropositive individuals will experience a symptomatic HSL recurrence, the frequency of which depends on genetic susceptibility, immune status, age, site of infection, and viral subtype (HSV-1 versus HSV-2) (3, 4). In most cases, patients with recurrent HSL experience minimal discomfort, pain, and disfigurement, but frequent outbreaks (Ͼ5 episodes/year, experienced by approximately 35% of patients with recurrent HSL) are associated with significant impact on physical, emotional, and social well-being (5).Recurrences of HSL differ from the primary/initial infection with respect to the roles that viral replication and inflammation play in the course of a lesion. In primary infection, lesion development, progression, and resolution are closely correlated with viral replication. In recurrent disease, lesion development and progression depend primarily on the proinflammatory host response (6) (Fig. 1). The central role of inflammation in lesion progression in recurrent disease may explain the limited efficacy of current antiviral monotherapy and suggests a new approach for more effective treatment. The value of one such approach, antiviral-anti-inflammatory combination treatment, has been demonstrated via several endpoints, including cumulative lesion area, a new efficacy endpoint. DUAL DISEASE PROCESSES IN HERPES SIMPLEX LABIALIS RECURRENCESRecurrent lesion development: correlations with viral processes. In recurrent HSL, HSV periodically reactivates (by mechanisms that are not completely understood) and moves from the cell body of latently infected sensory neurons toward the epidermis, where the virus begins to r...

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Section: Dual Disease Processes In Herpes Simplex Labialis Recurrencesmentioning

confidence: 99%

Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis

Hull

Levin

Tyring³

et al. 2014

Antimicrob Agents Chemother

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“…Iontophoretic delivery is controlled by pH of the applied formulation (degree of ionisation), current intensity, application time, permeant charge and presence of extraneous ions in the formulation [117]. Whilst iontophoresis is usually utilized as a means of enhancing transdermal delivery, its ability to enhance the dermal delivery of local anaesthetics [120] and antivirals [121,122] has been reported. Table 1 contains a list of some of the dermatological agents that have been successfully delivered using iontophoresis.…”

Section: Iontophoresismentioning

confidence: 99%

Topical Dermatological Drug Delivery: Quo Vadis?

Akomeah

2010

CDD

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Skin disease (dermatological conditions') affects at least one-third of the US population and has been cited as one of the top 15 medical conditions for which prevalence and healthcare spending increased in the last decade. The outcome of topical dermatological drug treatment is significantly influenced by the choice of vehicle or delivery system. Advancements in the life sciences coupled with a growing market for dermatologicals have facilitated the emergence of improved topical formulations and drug delivery systems. The current and emerging approaches of optimizing the topical delivery of dermatological agents (small and large molecules) include the use of chemical enhancers, bio-polymers (e.g. sodium hyaluronate), liposomes, particulate carriers (microspheres and lipid nanoparticles), topical sprays and foams, occlusion (via dressings and patches) topical peels, temperature (heat), iontophoresis and ultrasound. These delivery approaches (when used solely or in a synergistic manner) are a significant improvement over conventional systems (creams, lotions, ointments and pastes) and have the potential to enhance efficacy and tolerability, improve patient compliance (including dermatology life quality), and also fulfil other unmet needs of the topical dermatological market.

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“…17 Além dos dispositivos já prontos, contendo formulações otimizadas do fármaco, existem no mercado vários dispositivos em que o compartimento contendo o eletrodo é preenchido com uma solução aquosa do fármaco somente antes do uso. A Iomed desenvolveu uma grande quantidade deles baseados no sistema GelSponge ® , no qual os eletrodos permanecem embebidos em um hidrogel.…”

Section: Dispositivos Atualmente Utilizados E Possibilidades Futurasunclassified

“…2 Desde então a iontoforese é utilizada e extensivamente investigada para promover a liberação de fármacos através de vários epitélios, como mucosas, [4][5][6][7] cérvix, 8 olhos, 9-13 unhas 14,15 e, principalmente, pele [16][17][18][19][20][21][22][23][24] no tratamento de diversas patologias.…”

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Princípios básicos e aplicação da iontoforese na penetração cutânea de fármacos

Gratieri

Lopez

2008

Quím. Nova

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. do Café, s/n, 14040-903 Ribeirão Preto -SP, Brasil Recebido em 7/11/06; aceito em 20/9/07; publicado na web em 31/7/08 BASIC PRINCIPLES AND APPLICATIONS OF IONTOPHORESIS FOR CUTANEOUS PENETRATION OF DRUGS. Physicochemical constraints severely limit the number of molecules that can be considered as candidates for transdermal delivery. Iontophoresis is a non-invasive technique in which a weak electric current is used to enhance the penetration of molecules into or through the skin. In this review the underlying mechanisms that drive iontophoresis and the impact of key experimental parameters -namely, formulation, drug concentration and pH -on iontophoretic delivery efficiency are discussed. In the final section some devices that are currently commercialized are also described.Keywords: iontophoresis; topic and transdermal delivery; electrorepulsion. INTRODUÇÃOA aplicação da eletricidade em diferentes terapias remonta aos gregos, tendo sido explorada antes mesmo de seu descobrimento. 1Existem relatos do físico grego Aetius sobre a indicação de choques utilizando peixe elétrico para o tratamento de gota e hemorróida. Wiliam Gilbert, físico da rainha Elizabeth I, também se interessou pelo uso da eletricidade em tratamentos e publicou o livro "De Magneto", por volta de 1600. Mas foi em 1800 que Alexandro Volta provou que o fluxo de corrente elétrica ocorre entre dois metais semelhantes, quando colocados em contato, e atribuiu a este fenômeno a contração dos músculos da perna de sapo, observada em 1780 por Galvani. 2A aplicação de uma corrente elétrica fraca para transferir substâncias carregadas através de membranas biológicas, ou seja, a iontoforese, não é uma técnica nova. Ela foi primeiramente descrita por Veratti em 1748 e vem sendo modificada ao longo dos anos de acordo com as necessidades e capacidade tecnológica.3 No final do século XIX, Morton escreveu um livro sobre a cataforese de íons nos tecidos, isto é, a migração de cátions de um eletrodo positivo em direção a um eletrodo de polaridade negativa. Neste livro o autor descreve um experimento conduzido em seu próprio braço. Nele, grafite em pó foi colocada em contato com um eletrodo positivo e a aplicação de uma corrente elétrica provocou o aparecimento de pequenas manchas pretas no local, que persistiram por várias semanas. No início do século XX, Leduc mostrou que a iontoforese poderia ser usada para levar princípios ativos através da pele usando dois coelhos conectados em série a um gerador de corrente. Soluções de estricnina e de cianeto foram colocadas em contato com a pele dos animais e uma corrente elétrica foi aplicada. Sem a aplicação da corrente elétrica nada aconteceu aos coelhos. No entanto, após a aplicação da corrente, o coelho ao qual foi aplicada estricnina apresentou convulsões tetânicas, enquanto o segundo morreu apresentando sintomas de envenenamento por cianeto.2 Desde então a iontoforese é utilizada e extensivamente investigada para promover a liberação de fármacos através de vários epitélios, como mucosas, 25-27 A iontoforese apresent...

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Topical Iontophoretic Administration of Acyclovir for the Episodic Treatment of Herpes Labialis: A Randomized, Double-Blind, Placebo-Controlled, Clinic-Initiated Trial

Abstract: Single-dose topical iontophoresis of acyclovir appears to be a convenient and effective treatment for cold sores and merits further clinical investigation.

Cited by 31 publications

References 23 publications

Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis

Novel Composite Efficacy Measure To Demonstrate the Rationale and Efficacy of Combination Antiviral–Anti-Inflammatory Treatment for Recurrent Herpes Simplex Labialis

Topical Dermatological Drug Delivery: Quo Vadis?

Princípios básicos e aplicação da iontoforese na penetração cutânea de fármacos

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