penciclovir and Herpes-Genitalis

The herpesviruses continue to produce considerable morbidity in man. Once infected with herpes simplex (HSV), the virus remains dormant within the nervous system and may reactivate if provoked by stress, trauma and/or other factors. To date, there is no cure, but antiviral medication can reduce duration and severity of symptoms and prophylaxis can suppress recurrent episodes of disease. The second-generation guanosine nucleosides, acyclovir and penciclovir, are effective inhibitors with low toxicity; both, however, have relatively low oral bioavailability. Subsequently, the orally bioavailable prodrugs valaciclovir and famciclovir have been introduced. These compounds offer high oral bioavailabilty and deliver acyclovir and penciclovir, respectively, to the target cells by means of more convenient dosing schedules. This short review points to recent experience with famciclovir in the management of HSV and varicella-zoster virus.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Biological Availability; Clinical Trials as Topic; Famciclovir; Guanine; Herpes Genitalis; Herpes Zoster; Humans; Male; Nervous System; Prodrugs

Genital herpes is one of the most widespread sexually transmitted diseases in the world. HSV2 predominates (60-80 p. 100), but the prevalence of HSV1 genital herpes is rising (20-40 p. 100). Erosive lesions of the genital organs due to HSV infection are a factor favoring HIV contamination and other sexually transmitted diseases. The main factor of transmission is asymptomatic viral excretion. Aciclovir, valaciclovir and famciclovir are effective treatment for genital herpes (primary infection, curative and preventive treatment of recurrence), but none of these compounds alters the natural history of the infection. Aciclovir given as a preventive measure reduces the load of asymptomatic viral excretion. Information and education of patients with genital herpes are key elements for prevention. Use of preservatives appears to be effective. New vaccine strategies favoring humoral and cellular response should be studied.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Drug Therapy, Combination; Famciclovir; Female; France; Guanine; Herpes Genitalis; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Patient Education as Topic; Risk Factors; Valacyclovir; Valine; Virus Shedding

Topics: Acyclovir; Administration, Topical; Antioxidants; Antiviral Agents; Butylated Hydroxytoluene; Drug Therapy, Combination; Guanine; Herpes Genitalis; Herpes Labialis; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Interferon-alpha; Vidarabine

The current arsenal of antiviral agents available to the practitioner is expanding rapidly, such that by the time this article goes to press, new drugs may have already been added. Although the majority of approved drugs have been developed for use in only a few viral infections (eg, HIV, herpesviruses, and papillomavirus), discoveries made in the development of these drugs may lead to antiviral agents effective against other viruses. In addition, new uses for the currently available drugs are under evaluation. This review of antiviral agents discusses the treatments available for viral infections such as herpes simplex virus, varicella zoster virus, cytomegalovirus, human papillomavirus, chronic viral hepatitis, and others.

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Famciclovir; Foscarnet; Guanine; Hepatitis B; Hepatitis C; Herpes Genitalis; Herpes Simplex; Herpesvirus 3, Human; Herpesvirus 8, Human; Humans; Papillomavirus Infections; Sarcoma, Kaposi; Skin Diseases, Viral; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Famciclovir; Guanine; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Prodrugs; Simplexvirus; Virus Replication

Topics: 2-Aminopurine; Acyclovir; Antiviral Agents; Famciclovir; Guanine; Herpes Genitalis; Humans; Recurrence

Genital herpes simplex virus (HSV) infection, a sexually transmitted disease (STD), is the commonest cause of ulcerative genital infections among the young and adult population. The significant association of genital ulceration and transmission of human immunodeficiency virus (HIV) has been shown in many studies. To explore the potential efficacy of topical treatment of genital herpes with penciclovir cream, a randomized, double-blind, multicentre, acyclovir-controlled Phase II clinical trial of penciclovir 1% cream 5 times daily up to 7 days for suppression of genital herpes was conducted in China. A total of 205 patients aged 20-59 years (mean age 36.0+/-8.8 years for acyclovir and 34.8+/-8.4 years for penciclovir) with a clinical diagnosis of genital herpes were randomly allocated to one of the 2 parallel treatment groups and used for analysis. Clinical assessment were made before treatment and followed up at every visit during the study. Our results show that there was an encouraging improvement simultaneously in the 2 groups although no significant differences in clinical efficacy with respect to clinical cure rate, and times to healing, resolution of all symptoms, absence of blisters, cessation of new blisters, crusting, and loss of crust between penciclovir and acyclovir groups in terms of primary, non-primary and total patients were found. However a significantly shorter time to crusting was found in primary penciclovir group when compared with primary acyclovir group. Adverse experience was generally infrequent and mild, and was comparable in the 2 treatment groups. Based on these preliminary clinical findings, further evaluation of penciclovir 3% cream for topical treatment of genital herpes is planned.

Topics: Acyclovir; Administration, Topical; Adult; Antiviral Agents; China; Double-Blind Method; Female; Follow-Up Studies; Guanine; Herpes Genitalis; Humans; Male; Middle Aged; Proportional Hazards Models; Recurrence; Time Factors; Treatment Outcome

To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes.. In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences.. The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy.. Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Adult; Antigen-Antibody Complex; Antiviral Agents; Double-Blind Method; Famciclovir; Female; Guanine; Herpes Genitalis; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Recurrence; Simplexvirus; Treatment Outcome

The Chinese Herbal Prescription JieZe-1(JZ-1), added and subtracted from Yihuang Decoction, a famous formula in the 12th year of Kangxi in Qing Dynasty, has a clear effect on Genital Herpes (GH) and no obvious adverse reactions occur clinically. JZ-1 also has preventive and therapeutic effects on Trichomonas vaginitis, Candida albicans vaginitis and GH in vitro and in vivo experiments.. The effect and mechanism of JZ-1 on anti-herpes simplex virus type 2(HSV-2) in vitro focusing on adhesion and penetration stages were investigated.. A model of HSV-2 infection of VK2/E6E7 was developed. In order to explore JZ-1's anti-HSV-2 effect in vitro, cell morphology, ultrastructural pathology, cell viability and expression of viral glycoprotein D (gD) were assessed at 6 h, 12 h, 18 h, and 24 h of JZ-1 treatment. Then we measured the exact time required for adhesion and penetration of HSV-2 into VK2/E6E7 among a series of times at room temperature and under temperature control techniques. We treated VK2/E6E7 with JZ-1, penciclovir, or berberine and explored the mechanism of JZ-1 in blocking HSV-2 adhesion and penetration of host cells by assessing the cell ultrastructural pathology, viability, viral proteins gB, gD, VP16, ICP5, and ICP4 and host cell proteins HVEM, Nectin-1, and Nectin-2.. HSV-2 can fully adhere and penetrate into VK/E6E7 within 5 mins at room temperature while it takes 60mins under temperature control techniques. JZ-1 and penciclovir showed significant anti-HSV-2 effects, with improved host cell morphologies and increased host cell viabilities observed after treatment for 24 h. The anti-HSV-2 effect of JZ-1 can be detected after treatment for 6 h while that of penciclovir was not obvious until treatment for 12 h. JZ-1 showed distinct effect on HSV-2 adhesion and penetration stages by significantly reducing the expression of viral proteins gB, gD, VP16, ICP5, and ICP4, improving cell morphology and increasing cell viability. However, these effects were not exerted via downregulated expression of membrane fusion-related proteins such as HVEM, Nectin-1, or Nectin-2. The specific anti-HSV-2 mechanism of JZ-1 need to be further explored.. The anti-HSV-2 effect of JZ-1 was superior to that of penciclovir and berberine in vitro, and was mainly mediated by enhancing host cell defense and blocking adhesion and penetration of HSV-2.

Topics: Acyclovir; Antiviral Agents; Berberine; Cell Line; Drugs, Chinese Herbal; Epithelial Cells; Female; Guanine; Herpes Genitalis; Herpesvirus 2, Human; Humans; Vagina; Virus Attachment; Virus Internalization

A series of tricyclic penciclovir (PCV) and hydroxybutylguanine (HBG) derivatives have been prepared with enhanced lipophilicity following an efficient synthetic route. All the novel tricyclic derivatives were evaluated for inhibitory activity against herpes simplex virus 1 and 2 (HSV-1, HSV-2) and thymidine kinase deficient (ACV resistant) HSV-1. The tricyclic HBG derivatives were devoid of inhibitory activity however several of the tricyclic PCV derivatives showed promising antiviral activity, in particular 9g (R = 4-MeO-C

Topics: Acyclovir; Antiviral Agents; Guanine; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Models, Molecular

Herpes simplex virus type 2 (HSV-2) resistance to antiviral drugs has been described primarily in immunocompromised patients. We report an apparently immunocompetent, human immunodeficiency virus-negative male patient who has experienced repeated HSV-2 genital outbreaks despite receiving antiviral prophylaxis with several different drugs. Several of the HSV-2 genital isolates from this patient have been confirmed as resistant to acyclovir and penciclovir. Antiviral resistance occurred in the setting of long-term prednisone treatment and intermittent acyclovir prophylaxis at suboptimal doses and persisted despite the cessation of oral steroid treatment. The patient's genital herpes outbreaks were not controlled by high-dose prophylaxis with acyclovir, valacyclovir, and famciclovir. Cessation of antiviral prophylaxis resulted in reversion of this patient's HSV-2 isolates to acyclovir and penciclovir sensitivity, although resistant virus reappeared when antiviral prophylaxis was resumed. Transmission of a sensitive HSV-2 strain from this patient to a female sex partner was observed. These observations confirm previous reports that resistance to acyclovir may develop during prophylactic therapy in an otherwise well, immunocompetent patient. These findings support the conclusion that both drug-sensitive and drug-resistant HSV-2 strains established latency in this patient and that both strains are capable of frequent reactivation.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Multiple, Viral; Female; Guanine; Herpes Genitalis; Herpesvirus 2, Human; Humans; Immunocompetence; Male; Recurrence

A heterogeneous herpes simplex virus type 2 (HSV-2) population was characterised from an AIDS patient with relapsing genital ulcer. The isolate had an unusual antiviral spectrum, showing resistance to penciclovir and susceptibility to acyclovir. Two viral populations were plaque purified, one resistant and the other susceptible to both antiviral drugs. The resistant clone was deficient in thymidine kinase (TK) activity and a nucleotide substitution, thymine for cytosine, at position 153 was identified in its TK gene. This mutation resulted in an amino acid change, arginine to tryptophan, in the ATP binding site. In the deficient mutant, a loss of virulence was observed in mice.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Amino Acid Substitution; Animals; Antiviral Agents; Base Sequence; Chlorocebus aethiops; DNA, Viral; Drug Resistance, Viral; Female; Genes, Viral; Guanine; Herpes Genitalis; Herpesvirus 2, Human; Humans; Male; Mice; Thymidine Kinase; Vero Cells; Virulence

The antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2'-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.

Topics: Acyclovir; Administration, Oral; Animals; Antiviral Agents; Female; Guanine; Guinea Pigs; Half-Life; Herpes Genitalis; Humans; Injections, Intraperitoneal; Oleic Acid; Oleic Acids; Recurrence; Urinary Retention; Vagina

The immunosuppressive agent mycophenolate mofetil (MMF) has been approved for use in kidney transplant recipients and may thus be used concomitantly for the treatment of intercurrent herpesvirus infections with drugs such as acyclovir (ACV), ganciclovir (GCV), and penciclovir (PCV). We found that MMF and its parent compound mycophenolic acid (at concentrations that are attainable in plasma) strongly potentiate the antiherpesvirus (herpes simplex virus [HSV] type 1 [HSV-1], HSV-2, thymidine kinase-deficient [TK-] HSV-1, both wild-type and TK- varicella-zoster virus, and human cytomegalovirus) activities of ACV, PCV, and GCV (up to 350-fold increases in their activities). The mechanism of potentiation was found to reside in the depletion of endogenous dGTP pools, which favored the inhibitory effect of the triphosphate of ACV, GCV, or PCV on the viral DNA polymerase. The combination of topically applied 5% MMF with 0.1% ACV strongly protected against HSV-1-induced cutaneous lesions in hairless mice, whereas therapy with either compound used singly had no protective effect. Interestingly, the combination of topically applied 5% MMF with 5% ACV was also highly effective in protecting against TK- HSV-2-induced cutaneous lesions (that were refractory to ACV treatment) in athymic nude mice. Topical therapy with MMF was very well tolerated, and no signs of irritation were observed. When given perorally at 200 mg/kg of body weight/day, MMF potentiated to some extent the growth retardation induced by GCV in young NMRI mice. These observations may have clinical implications (i) for those transplant recipients who receive both MMF and either ACV, GCV, or PCV and (ii) for the treatment of ACV-resistant mucocutaneous HSV infections.

Topics: Acyclovir; Animals; Antiviral Agents; Cells, Cultured; Chlorocebus aethiops; Deoxyguanine Nucleotides; Drug Synergism; Drug Therapy, Combination; Ganciclovir; Guanine; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Immunosuppressive Agents; Mice; Mice, Nude; Mycophenolic Acid; Vero Cells