Topical Acyclovir Research Articles

Acanthamoeba epitheliopathy: Atypical presentation of Acanthamoeba keratitis

To report clinical features of the epithelial stage of Acanthamoeba keratitis to highlight the impact of an early diagnosis on outcome. A 42-year-old male, with a recurrent history of symptoms and a history of pond water bathing, presented with a linear non-branching epithelial lesion that stained poorly with fluorescein. He was diagnosed with herpes simplex epithelial keratitis and treated with topical acyclovir. However, a ring-like stromal infiltrate developed, and microbiology evaluation revealed Acanthamoeba cysts. Although the disease progressed significantly despite treatment with topical amoebicidal agents, it finally resolved. A 26-year-old male, with an antecedent history of trauma, presented with a ring-like epithelial lesion only, and microbiology evaluation revealed Acanthamoeba cysts. He was treated with topical chlorhexidine 0.02%, and the lesions healed without stromal progression. A delayed diagnosis in the first patient led to a poorer outcome, while an early diagnosis in the second patient led to a better outcome.

Prevalence and healthcare utilization in managing herpes zoster in primary care: a retrospective study in an Asian urban population.

Herpes zoster (HZ) causes significant morbidity, particularly in older adults. With the advent of a recombinant zoster vaccine, HZ is potentially preventable. However, data on HZ burden and healthcare utilization in primary care populations remains scarce. This study described the prevalence and healthcare utilization in managing HZ in a developed community. A retrospective database review was conducted across a cluster of 8 public primary care clinics in urban Singapore. Data of multi-ethnic Asian patients with a diagnosis code of "herpes zoster" from 2018 to 2020 was extracted from their electronic medical records. Socio-demographic, clinical, visitation, medical leave, prescription, and referral data were analyzed. A total of 2,987 out of 737,868 individuals were diagnosed with HZ over 3 years. The mean age was 59.9 (SD + 15.5) years; 49.2% were male; 78.5% Chinese, 12.2% Malay, and 4.1% Indian. The prevalence was 221, 224, 203 per 100,000 persons in 2018, 2019, and 2020, respectively. The 70 to 79-year age group had the highest prevalence (829/100,000) across 3 years. Oral acyclovir (median daily dose 4,000 mg; median duration 7 days) and topical acyclovir were prescribed in 71.6 and 47.6%, respectively. Analgesia prescribed were gabapentin (41.0%), paracetamol combinations (30.1%), oral NSAIDs (23.7%), opioids (6.0%), and tricyclic antidepressants (1.9%). Most individuals consulted only once (84.3%); 32.7% of them required medical leave and 5.6% had more than 7 days of absenteeism. HZ-related referrals to the hospital were required in 8.9% (4.9% emergency, 2.8% ophthalmology). The findings of this study suggest a need for HZ vaccination among older age groups. Visitation and referral rates were low. The use of topical acyclovir was uncovered, and further research should evaluate the underlying reasons, benefits, and harms of such practice. The use of analgesia combinations may be explored further.

Detailed pharmacokinetic characterization of advanced topical acyclovir formulations with IVPT and in vivo Open Flow Microperfusion

Successful treatment of herpes simplex viruses is currently limited by a lack of effective topical drugs. Commonly used topical acyclovir products only reduce the duration of lesions by a few days. Optimizing topical formulations to achieve an enhanced acyclovir solubility and penetration could increase the efficacy of topically applied acyclovir, but new formulations need to show reliable acyclovir delivery into at least the epidermis/dermis and need to provide sustained acyclovir release for extended time periods. The aim of this study was to compare pharmacokinetic data from in vitro permeation testing (IVPT) and preclinical dermal open flow microperfusion (dOFM) experiments regarding the penetration behavior of different acyclovir formulations relative to the reference product Zovirax® 5% cream. Four test formulations that delivered the best penetration data in IVPT were further tested using continuous dOFM in vivo dermal sampling. The use of dOFM identified one of the four tested formulations to perform significantly better than the other three tested formulations and the reference product. In vivo dOFM data showed differences in the dermal acyclovir concentration that had not been detected by using IVPT. Improved acyclovir delivery to the dermis was likely achieved by the new formulation that uses a much lower drug load compared to the reference product. This optimized formulation was able to achieve a dermal concentration similar to oral application and can thus provide the opportunity of more efficacious topical HSV-1 treatment with less side effects than oral systemic treatment.

Development and Assessment of Acyclovir Gel Plaster Containing Sponge Spicules

Acyclovir is an acyclic purine nucleoside analog that is highly effective in inhibiting the herpes simplex virus. However, topical acyclovir has poor efficacy because of its low skin permeability. This study aimed to develop an acyclovir gel plaster containing sponge spicules (AGP-SS) to achieve synergistic improvements in skin absorption and deposition of acyclovir. The process of preparing the gel plaster was optimized by orthogonal experiments, while the composition of the formulation was optimized using the Plackett-Burman and Box–Behnken experimental designs. The selected formula was tested for physical properties, in vitro release, stability, ex vivo permeation, skin irritation, and pharmacokinetics. The optimized formulation exhibited good physical characteristics. In vitro release and ex vivo permeation studies showed that acyclovir release from AGP-SS was dominated by diffusion with significantly higher skin permeation (20.00 ± 1.07 μg/cm2) than that of the controls (p < 0.05). Dermatopharmacokinetic analyses revealed that the maximum concentration (78.74 ± 11.12 μg/g), area under the curve (1091.81 ± 29.05 μg/g/h) and relative bioavailability (197.12) of AGP-SS were higher than those of the controls. Therefore, gel plaster containing sponge spicules show potential for development as transdermal delivery systems to achieve higher skin absorption and deposition of acyclovir, especially in deep skin layers.

Antiviral treatment in outpatients with herps zoster in six major areas of China, 2010-2019.

ObjectiveThe objective of this study was to assess the status and trends of antiviral treatment in outpatients with herpes zoster in China.MethodsPrescription data on antiviral drugs were extracted from the database of the Hospital Prescription Analysis Program of China according to the inclusion criteria. Yearly prescriptions and costs were calculated, and trends were analyzed. The trends were further stratified by age, sex, and specific drug use. The distribution of defined daily costs (DDCs) of valaciclovir and famciclovir were analyzed, and trends in the median DDCs were identified.ResultsA total of 132,911 prescriptions from 49 hospitals located in six major areas of China were included in the analysis. The yearly prescriptions containing antivirals increased from 8,819 in 2010 to 16,361 in 2019. The percentage of prescriptions for patients aged 65 years and above also increased (27.7% in 2010 to 31.0% in 2019), and the number of prescriptions for females was higher than those for males (P < 0.001). The average cost of antivirals per prescription decreased; thus, the yearly cost showed no increasing trend. The main prescribed antivirals were valaciclovir and famciclovir, which progressively increased in prescriptions. The use of acyclovir decreased during the study period. Prescriptions containing topical formulations, acyclovir and penciclovir, both increased. The DDCs of valaciclovir and famciclovir decreased dramatically.ConclusionThe use of antivirals has increased over the decade, while the cost has not. Antiviral treatments adhere well to recent recommendations, except for the use of topical antivirals. The findings of this study may benefit the healthcare source allocation and management of herpes zoster in China.

Application of Confocal Raman Microscopy for the Characterization of Topical Semisolid Formulations and their Penetration into Human Skin Ex Vivo

PurposeThe quality testing and approval procedure for most pharmaceutical products is a streamlined process with standardized procedures for the determination of critical quality attributes. However, the evaluation of semisolid dosage forms for topical drug delivery remains a challenging task. The work presented here highlights confocal Raman microscopy (CRM) as a valuable tool for the characterization of such products.MethodsCRM, a laser-based method, combining chemically-selective analysis and high resolution imaging, is used for the evaluation of different commercially available topical acyclovir creams.ResultsWe show that CRM enables the spatially resolved analysis of microstructural features of semisolid products and provides insights into drug distribution and polymorphic state as well as the composition and arrangement of excipients. Further, we explore how CRM can be used to monitor phase separation and to study skin penetration and the interaction with fresh and cryopreserved excised human skin tissue.ConclusionThis study presents a comprehensive overview and illustration of how CRM can facilitate several types of key analyses of semisolid topical formulations and of their interaction with their biological target site, illustrating that CRM is a useful tool for research, development as well as for quality testing in the pharmaceutical industry.Graphical abstract

Presumed herpes simplex virus ulcerative nodular episcleritis treated by topical acyclovir alone

A 7-year-old female child was referred to the cornea clinic with a painless, ulcerated, and inflamed nodule near the limbus which did not respond to 1-week antibiotic therapy and worsened on starting topical steroids. Clinical examination showed ulcerative nodular episcleritis and raised a suspicion of herpes simplex virus etiology. The patient responded well and resolved completely on topical antiviral therapy alone.

Comparison of topical acyclovir and penciclovir in recurrent herpes labialis treatment

Purpose: The aim of this study is to compare the effects of acyclovir and penciclovir creams in the treatment of recurrent herpes labialis. &#x0D; Materials and Methods: Seventy patients with pre-diagnosed recurrent herpes labialis lesions were enrolled in this study. Diagnosis was confirmed with HSV-1 IgM antibody test. Patients were separated under 2 treatment groups as acyclovir and penciclovir cream. Both agents were applied until complete healing of the lesions was seen. Burning, itching and bleeding scores; time of erythema, vesicles, ulceration, crusting and crust loss of the lesions were recorded. Pain values of the patients were recorded using a visual analog scale (VAS) and DASS-21 scale was used to measure emotional state related to depression, anxiety and stress. &#x0D; Results: Pain level in the acyclovir group was significantly lower than the penciclovir group in the 3rd day, though with no difference in the following days. DASS-21 scores revealed signs of depression on 62.8% of the patients, anxiety on 34.2% of the patients, and stress on 41.4% of the patients in moderate or higher levels. While the pain level was higher in patients with high anxiety severity, it was observed that the pain level was low in patients with high stress intensity.&#x0D; Conclusion: Although it is not possible to cure recurrent herpes labialis completely, any methods and drugs that shorten the healing time of the lesion and reduce pain and discomfort gains importance. Our study showed that acyclovir is superior in reducing pain.

HERPES ASSOCIATED ERITHEMA MULTIFORME (HAEM ) ON THE PSYCHOSOMATIC PATIENT : A CASE REPORT

Background : Erythema multiforme is an acute mucocutaneous inflammation which is self limiting desease. One of caused of Erythema multiforme is Herpes Simplex Virus infection diagnosed as Herpes Associated Erytema Multiforme (HAEM). The psychosomatic patients should be wary of anti-depressant therapy, because if there is an allergy, it can trigger the occurrence of erthema multiformis. In this paper, we will reported HAEM case on psychosomatic patient.Case and management : A case of 23 years old female patient with chief complaint sore and pain lips since one weeks ago. The patient has been on anti-depressant therapy for one month. Clinical examination on patient showed that there were erosive lesion covered by reddish brown crusta, sloughing on the border between lips and labial mucosa, and bloody lips. The results of laboratory tests show positive HSV. Patient was diagnosed with HAEM. Therapy given to the patient was corticosteroid topical oitment, acyclovir and oral rinse antiseptics. After two weeks the administration, condition on the patient has improved.Conclusions : HAEM cases if treated properly can recover well. Trigger factors must be controlled so that not recurrance

Conjunctival herpetic ulcer in an immunosuppressed patient with birdshot chorioretinopathy

Introduction: Herpes Simplex Virus (HSV) is a human herpesvirus responsible for systemic infections. Ocular involvement spans all ocular tissues. Corneal lesions, such as dendritic or geographic ulcers, are frequently found in HSV keratitis while conjunctival lesions have been described as infrequent.&#x0D; Clinical case: A 62-year-old man diagnosed with Birdshot chorioretinopathy presented a stye in his eyelid that was treated with oxytetracycline-hydrocortisone ointment. One week later he returned presenting several small dendritic corneal ulcers in both eyes and a conjunctival ulcer in one of them. All lesions healed completely after treatment with topical acyclovir ophthalmic ointment at 3%.&#x0D; Conclusions: We should pay attention to the conjunctiva and not merely focus on the cornea when examining patients with herpetic eye disease, especially if being treated with inmunosupressors.

HERPES SIMPLEX VIRUS (HSV) KERATITIS BILATERAL WITH FILAMENTOUS

Introduction : Herpetic keratitis is caused by herpes simplex virus and is a common cause of corneal blindness. Generally herpes simplex keratitis is a unilateral disease, but bilateral disease has been reported in 1,3 % to 10,9 % of patients. Filamentous keratitis most often caused by dry eye, especially aqueous tear-deficient dry eye. Objective: To report a case of bilateral herpes simplex virus keratitis bilateral with filamentous. Method: A 45 years old man was admitted to Dr. M. Djamil Hospital Padang presented with glare and blurred on both eyes since 1 week ago. VA RE is 6/30, VA LE is 6/60. On ophthalmology examination were conjunctival and ciliary injection. On the cornea of both of eyes, found infiltrate numular shaped almost all of layer of the cornea. Cornea sensitivity was decreased on both eyes. Patient diagnosed by numularis keratitis of both eyes and therapy is oral and topical acyclovir. After 2 weeks therapy, we found filamentous on left eye. Debridement of filament was performed and the therapy was continued. Result: There are improvement of visual acuity and clinical feature. VA RE 6/15, LE 6/40. Subjectively, patient feel comfort. The sign of glare and photophobia are decrease. Density of infiltrate was decrease and no filamentous was found.

Comparison between Low Level Diode Laser Therapy and Acyclovir Cream 5% in Treatment of Herpes Labialis

Introduction: Recurrent Herpes Labialis (RHL) is a common infection and occurs in 20 to 40% of the general population. Risk for transmission exists in dental treatments. There are several different treatments for it. The purpose of this study is a comparison between low-level Laser therapy (LLLT) and acyclovir cream for the treatment of it. Materials &amp; Methods: This performed study was a semi-blind clinical trial in the Oral Medicine Department, Dental School, Islamic Azad University Isfahan Branch (Khorasgan) in the year 2015- 2016. 30 patients got divided into 2 similar groups. Patients in LLLT group, treated in 3 sessions every other day, received 660 nm laser irradiation,100mW,4 J/cm2, continuous, located at a distance of 1 mm from the lesion for 40 seconds. Patients in the medication group treated with 5% acyclovir cream five times a day. In both groups severity of pain and lesion size during treatment and healing time recorded. The collected data were analyzed using statistical tests including independent T-test and Repeated Measures ANOVA ( p value &lt; 0.05). Results: The laser group had better statistically findings for the median time for pain relief (p value &lt; 0.001), and the median time for healing (p value &lt; 0.001), the median lesions size two days after treatment (p value = 0.03), and four days after treatment (p value = 0.003). Conclusion: According to data analysis, laser 660 nm is more effective in pain relief and lesions size reduction and healing time than topical acyclovir in patients with herpes labialis.

Pathogenesis and chemotherapy of a thymidine kinase deficient mutant strain of HSV‐1 in a murine zosteriform infection model.

Type I and II Herpesvirus simplex virus [HSV] are contagious and cause oral (cold sores) and genital ulcers (genital HSV) before becoming latent in trigeminal ganglia (oral HSV) or sacral ganglia (genital HSV), and can reactivate and cause disease almost at the same spot of the initial virus exposure. Acyclovir is one of the gold standard treatments for labial and genital HSV for decades. Topical Acyclovir and penciclovir and their prodrugs act on thymidine kinase (TK) and are viral DNA chain inhibitor agents and hence inhibit virus replication. In TK deletion mutants, drugs which interact with TK enzyme and inhibit virus replication do not have any inhibitory effect. TK deletion mutants also replicate at slower rates and therefore take longer to make plaques in tissue culture compared to wild type strains. Resistant virus could also arise due to suboptimal treatment regimens although it is not a great problem currently in immunocompetent patients. However resistant HSV could be a major challenge to treat in immunocompromised and immunosuppressed patients as not many options are available to use antiviral drugs whose mode of action is to work on TK inhibition. In this study pathogenesis of TK deletion mutant resistant strains of HSV were used in a immunocompetent neck-ear zosteriform infection mouse model and efficacy of prodrugs on zoster spread was studied. Resistant strains of HSV mutants received were originally raised in vitro and plaques purified. These strains were then grown in tissue culture and working stock was produced. We observed that rate of replication of these mutant viruses was slower as they took longer to make plaque in tissue culture compared to wild type strains. Resistant strain of HSV were used in the immunocompetent murine zosteriform infection model along with the wild strain and efficacy of prodrugs was studied to see if murine immunocompetent natural defense will have any effect on the pathogenicity and if antiviral agents have any effect in vivo. A murine neck ear zosteriform infection model was used and development of zosteriform lesion were noted on the ear pinna along with ear thickness and body weight. Mutant viruses show delayed zosteriform spread. It was noticed that though lesions were not completely inhibited by prodrugs, zosteriform lesion and intensity was lower after antiviral treatment. This was not expected so we tend to believe that either immunocompetent immune defense system of mice were providing extra help to reduce the virus lesion or a possibility of helper virus in the murine model. In order to see the effect of TK activity in resistant mutants original stock was further analyzed by radiolabeled C-14 TK assay to confirm the deletion mutants status. In this communication In vivo results of zoster spread, radiolabeled C-14 TK assays to identify TK deletion mutant, purified cloning, other antiviral which can have an effect on TK deletion resistant HSV in immunocompromised and immunosuppressed patients will be discussed.

Effectiveness of photodynamic therapy as an adjunct to topical antiviral therapy in the treatment of herpes labialis: A randomized controlled clinical trial

BackgroundThe present clinical trial assessed the effectiveness of photodynamic therapy in association with topical acyclovir in the treatment of herpes labialis in adolescent patients. Materials and methods45 individuals with herpes labialis were divided into three groups on the basis of provision of treatment. (a) Group I: Topical acyclovir therapy (AVT) (n = 15, mean age: 17.5 years) (b) Group 2: photodynamic therapy (PDT) (n = 15, mean age:16.8 years) and (c) Group III: AVT + adjunctive PDT (n = 15, mean age: 17.0 years) respectively. HSV-1 quantification and pain scales [visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ)] were calculated. Pro-inflammatory biomarkers including interleukin (IL-6) and tumor necrosis factor-alpha (TNF-α) were quantified using enzyme linked immunosorbent assay (ELISA). Shapiro-Wilk test was used to assess the normality. The Friedman test was employed to compute the comparison for changes recorded in pain scores, proinflammatory cytokines and HSV-1 quantification, whereas Mann-Whitney test was used to analyze the mean values and establish inter-group comparisons. All assessments were performed at baseline, immediate post op, 2-weeks, 4-weeks, 3-months, and 6-months. ResultsA total of 44 individuals completed the clinical trial. According to the data obtained from the clinical assessment, all the study groups reported a decrease in the parameters being observed. However, Group III (anti-viral (acyclovir) therapy + adjunctive PDT) showed a statistically significant decrease, in comparison to Group II (PDT) and Group I [AVT] respectively. The quantified HSV-1 among all groups showed significant reduction among all groups at each successive follow-up. However, Group-III (AVT + PDT) showed statistically significant reduction as compared to Groups I and II, respectively (p < 0.05). ConclusionTopical anti-viral therapy with adjunctive PDT significantly helped in reducing the pain and pro-inflammatory biomarkers in adolescent herpes labialis patients.

Photodynamic therapy and Acyclovir in the treatment of recurrent herpes labialis: A controlled randomized clinical trial.

Herpes Simplex Virus Type 1 (HSV-1) is one of the most widespread infections that can effect the orofacial region. Recurrent infection is considered a life-long oral health problem, leading to pain, discomfort, and social restriction due to esthetic features when active. Effective therapies are needed. This study aimed to compare photodynamic therapy (PDT), Topical Acyclovir (AC), and the association of both in the healing process and self-reported symptomologies of HSV-1 recurrences. Patients were randomly assigned into 3 groups (n = 25): PDT (low-power laser, 660 nm, 40 mW, 120 J/cm2, 4.8 J, 120 s per point) and methylene blue (0.005 %) as photosensitizer; AC (5%); PDT + AC.Data concerning lesion size, healing time, and self-reported healing parameters, such as pain, tingling, and edema were taken every day up to complete healing for all studied groups. There was no significant difference in healing time and pain between groups. AC group showed a significant minor reduction of the lesion compared to the AC-PDT group on day 1. Regarding edema and tingling, the comparison of treatments showed a statistical difference only on day 1, where PDT showed better results. With all the limitations of this study, it can be concluded that only on day 1 PDT showed positive effects in the treatment of herpes lesions in comparison to AC.

Herpetic Keratouveitis following Intravitreal Ranibizumab Injection in a Case with Diabetic Macular Edema

ABSTRACT Purpose: The purpose of this study is to report a case of herpetic keratouveitis that developed soon after intravitreal ranibizumab injection. Case Report: A 54-year-old man with bilateral proliferative diabetic retinopathy and severe macular edema received intravitreal ranibizumab injections in both eyes within 3 days interval. One week after the injection, patient presented with acute vision loss in his right eye. Slit-lamp biomicroscopy revealed diffuse corneal edema and severe flare in the anterior chamber with intraocular pressure (IOP) rise. After epithelial dendritic corneal ulcer was visualized, he was diagnosed with right herpetic keratouveitis that was treated with oral valacyclovir, as well as topical acyclovir ointment and prednisolone acetate drops. However, recalcitrant IOP rise had to be treated with a single session transscleral diode laser cyclophotocoagulation. Conclusion: Herpetic keratouveitis can be seen as a rare complication of intravitreal ranibizumab injection. To our best knowledge, this is the first case with herpes keratouveitis developed following intravitreal ranibizumab injection.

A Novel Effect of Acyclovir on Hair Growth in BALB/c Mice: A Promising Future for Finding a New Topical Drug for the Treatment of Hirsutism.

PurposeHirsutism (ie, terminal hair growth on the face and body in a male-like pattern in women) is a common dermatological disorder in women, with psychosocial implications. Consequently, there is demand for finding novel pharmacological treatments and agents that can safely reduce hair growth. This study aimed to investigate the potential effect of topical acyclovir on hair growth in mice.MethodsIn this study, twenty-four female BALB/c mice were randomly divided into three groups in order to evaluate the hair growth-reducing effects of acyclovir (control group, vehicle group, and acyclovir group). Topical acyclovir 5% was applied on the shaved denuded skin of mice. Topical application onto the backs of the animals was performed twice daily for 28 consecutive days. The time (in days) required for hair growth initiation as well as completion of hair growth in dorsal skin of animals were recorded. On day 28, horizontally cut biopsy samples were removed and the numbers of hair follicles were counted, and the diameter of hair follicles was measured under high-field microscopy by a specialist blinded to the treatments.ResultsHair growth initiation time was significantly increased with acyclovir, as compared to control and vehicle groups. The time required for complete hair growth in control and vehicle groups were 18±0.68 and 19±1.41 days, respectively; however, the hair growth completion in acyclovir-treated animals was not observed at the end of the experiment. Furthermore, the length of hairs in treatment group was significantly shorter than the control group at the end of the study (P < 0.001). In histologic examination, the count and the diameter of hair follicles in deep subcutis were significantly decreased.ConclusionThe results of this study, for the first time, showed that topical administration of acyclovir might have inhibitory effects on hair growth in experimental animals; however, further studies are required to understand its mechanism.

Varicella-zoster virus-induced rhabdomyolysis: A case report and literature review

Infection is a possible cause of rhabdomyolysis. We describe the case of a 63-year-old male with malaise and erythematous papules on the right C5–C7 dermatomes, consistent with herpes zoster. Serum antibody and Tzanck tests of the skin lesion were positive. Increased serum creatine kinase (CK) and myoglobin levels and cola-colored urine indicated the development of rhabdomyolysis. Acute kidney injury was also observed. After excluding other possible predisposing factors, the patient was diagnosed with varicella-zoster virus (VZV)-induced rhabdomyolysis. Extracellular volume with alkalized fluids and topical acyclovir was administered. While CK levels declined to normal by day 13, the renal function was not restored. The skin lesion crusted by day 8 and scaled off gradually by day 13. Our case and literature review highlighted the necessity for systemic antiviral treatment and that poor VZV infection control could lead to irreversible kidney injury. In addition, systemic acyclovir should be administered carefully due to its complication of nephrotoxicity.

Period of excretion of equine herpesvirus 3 (EHV-3) from a stallion before showing clinical signs of equine coital exanthema and the effect of acyclovir treatment on the duration of EHV-3 excretion.

In 2017, two Thoroughbred stallions, A and B in Farms A and B, respectively, in Hokkaido in Japan showed clinical signs of equine coital exanthema (ECE). In 2020, stallion C in Farm B showed clinical signs of ECE. Eighteen mares were mated within five days before stallion A developed ECE. Ten mares that mated within 3 days before onset showed clinical signs of ECE on the external genitalia. Equine herpesvirus 3 (EHV-3) was isolated from vaginal swabs from three mares that mated within 2 days before onset. Swabs from 12 mares that mated within 4 days before onset were real-time PCR (rPCR)-positive and nine of those mares had an increased EHV-3 antibody titer. The three stallions were administered valaciclovir orally and topical acyclovir ointment was applied. Treatment started on the next day after onset in stallion A and on the day of onset in stallions B and C. EHV-3 was firstly isolated from penis swabs of stallions A and B before treatment and from penis swabs of stallion C 2 days after treatment. EHV-3 was not isolated after 8, 5 and 8 days from onset in stallions A, B and C, respectively. However, swabs were rPCR-positive for at least 12, 9 and 15 days after onset of stallions A, B and C, respectively. EHV-3 was excreted from the stallions at least within 4 days before the onset of ECE, and acyclovir treatment resulted in the termination of excretion within 8 days after onset.

Stratum Corneum Sampling to Assess Bioequivalence between Topical Acyclovir Products

PurposeTo examine the potential of stratum corneum (SC) sampling via tape-stripping in humans to assess bioequivalence of topical acyclovir drug products, and to explore the potential value of alternative metrics of local skin bioavailability calculable from SC sampling experiments.MethodsThree acyclovir creams were considered in two separate studies in which drug amounts in the SC after uptake and clearance periods were measured and used to assess bioequivalence. In each study, a “reference” formulation (evaluated twice) was compared to the “test” in 10 subjects. Each application site was replicated to achieve greater statistical power with fewer volunteers.ResultsSC sampling revealed similarities and differences between products consistent with results from other surrogate bioequivalence measures, including dermal open-flow microperfusion experiments. Further analysis of the tape-stripping data permitted acyclovir flux into the viable skin to be deduced and drug concentration in that ‘compartment’ to be estimated.ConclusionsAcyclovir quantities determined in the SC, following a single-time point uptake and clearance protocol, can be judiciously used both to objectively compare product performance in vivo and to assess delivery of the active into skin tissue below the barrier, thereby permitting local concentrations at or near to the site of action to be determined.