Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption.

OBJECTIVE: To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana). ANIMALS: 15 African elephants (6 males and 9 females) of various ages. METHODS: Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling. RESULTS: Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 µg·h/mL), maximum observed concentration (Cmax; 3.73 µg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 µg·h/mL; Cmax, 2.52 µg/mL; and absorption t1/2, 0.13 hours. CONCLUSIONS: Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration. CLINICAL RELEVANCE: African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.

Molecular interaction of antiviral drug penciclovir with DNA and HSA insights from experimental and docking studies.

One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. During recent decades, penciclovir (PNV) has been frequently utilized as a potent antiviral drug, in particular against infections caused by herpes viruses. Many antivirals interact with DNA and change their expression level, so determining the binding mode is of great importance. In our laboratory, we have focused our attention to design improved drugs that target cellular DNA, to understand the mechanism of action at the molecular level, and also to investigate the effect of antiviral drugs as anticancer agents. The results of ct-DNA-PNV interactions at physiological pH using fluorescence spectroscopy, UV-visible absorption spectroscopy, and molecular modeling reveal this drug binds well to ct-DNA through groove binding. The circular dichroism measurements displayed that PNV caused a slight change in the DNA structure which affirmed that the binding of PNV with the DNA occurs through the groove mode. Besides, multi-spectroscopic and molecular docking were used to evaluate how PNV interacts with human serum albumin under physiological conditions. The findings of fluorescence quenching suggested that static quenching was involved in the spontaneous development of HSA-PNV complex through hydrophobic force. The docking simulation results validated the findings of spectroscopic techniques.Communicated by Ramaswamy H. Sarma.

Optimization of Thymidine Kinase-Based Safety Switch for Neural Cell Therapy.

Cell therapies based on pluripotent stem cells (PSC), have opened new therapeutic strategies for neurodegenerative diseases. However, insufficiently differentiated PSC can lead to tumor formation. Ideally, safety switch therapies should selectively kill proliferative transplant cells while preserving post-mitotic neurons. In this study, we evaluated the potential of nucleoside analogs and thymidine kinase-based suicide genes. Among tested thymidine kinase variants, the humanized SR39 (SR39h) variant rendered cells most sensitive to suicide induction. Unexpectedly, post-mitotic neurons with ubiquitous SR39h expression were killed by ganciclovir, but were spared when SR39h was expressed under the control of the cell cycle-dependent Ki67 promoter. The efficacy of six different nucleoside analogs to induce cell death was then evaluated. Penciclovir (PCV) showed the most interesting properties with an efficiency comparable to ganciclovir (GCV), but low toxicity. We tested three nucleoside analogs in vivo: at concentrations of 40 mg/kg/day, PCV and GCV prevented tumor formation, while acyclovir (ACV) did not. In summary, SR39h under the control of a cell cycle-dependent promoter appears most efficient and selective as safety switch for neural transplants. In this setting, PCV and GCV are efficient inducers of cell death. Because of its low toxicity, PCV might become a preferred alternative to GCV.

Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2.

COVID-19, for which no confirmed therapeutic agents are available, has claimed over 48,14,000 lives globally. A feasible and quicker method to resolve this problem may be 'drug repositioning'. We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals. These drugs were docked onto the nsp12 protein, which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2, a key therapeutic target for coronaviruses. Docked complexes were reevaluated using MM-GBSA analysis and the top three inhibitor-protein complexes were subjected to 100 ns long molecular dynamics simulation followed by another round of MM-GBSA analysis. The RMSF plots, binding energies and the mode of physicochemical interaction of the active site of the protein with the drugs were evaluated. Suramin, Penciclovir, and Anidulafungin were found to bind to nsp12 with similar binding energies as that of Remdesivir, which has been used as a therapy for COVID-19. In addition, recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2. Such evidence, along with the significant and varied physical interactions of these drugs with the key viral enzyme outlined in this investigation, indicates that they might have a prospective therapeutic potential in the treatment of COVID-19 as monotherapy or combination therapy with Remdesivir.

Inspection on the Mechanism of SARS-CoV-2 Inhibition by Penciclovir: A Molecular Dynamic Study.

In recent years, humanity has had to face a critical pandemic due to SARS-CoV-2. In the rapid search for effective drugs against this RNA-positive virus, the repurposing of already existing nucleotide/nucleoside analogs able to stop RNA replication by inhibiting the RNA-dependent RNA polymerase enzyme has been evaluated. In this process, a valid contribution has been the use of in silico experiments, which allow for a rapid evaluation of the possible effectiveness of the proposed drugs. Here we propose a molecular dynamic study to provide insight into the inhibition mechanism of Penciclovir, a nucleotide analog on the RNA-dependent RNA polymerase enzyme. Besides the presented results, in this article, for the first time, molecular dynamic simulations have been performed considering not only the RNA-dependent RNA polymerase protein, but also its cofactors (fundamental for RNA replication) and double-strand RNA.

Variable accuracy, precision, and consistency of compounded famciclovir formulated for management of feline herpesvirus-1 in cats.

OBJECTIVE: To evaluate compounded famciclovir suspensions for accuracy, precision, and consistency in drug content. PROCEDURES: Two compounded famciclovir concentrations were evaluated (250 and 400 mg/mL, 30 preparations total from nine 503A compounding pharmacies) with U.S. Food and Drug Administration (FDA)-approved famciclovir tablets as control. Drug quantification via high-performance liquid chromatography (with famciclovir reference standard and pramipexole internal standard) was performed at 0, 14, and 28 days with concentrations of 90%-110% of labeled dose considered acceptable (US Pharmacopoeia standards). RESULTS: FDA-approved tablets from three different manufacturers were found to be accurate and precise with acceptable drug content. A significantly greater mean deviation from labeled content was noted for 400 mg/mL suspensions (-52.9%) compared to 250 mg/mL suspensions (-18.0%). When assessing time points separately, 15/63 (24%) samples of 250 mg/mL and 0/27 (0%) samples of 400 mg/mL suspensions met the acceptance standards. Coefficients of variation (CV) in drug content among pharmacy batches ranged from 0.5% to 29%, with 5/10 formulations having significantly lower CV% compared to control (decreased precision). Similarly, drug content changed over time (0-28 days) in all compounded formulations, with both downward and upward trends observed (variable consistency). CONCLUSIONS: Most compounded famciclovir formulations were inaccurate, imprecise, and inconsistent. FDA-approved famciclovir tablets may be preferred over compounded famciclovir formulations for the management of feline herpesvirus-1. If compounded famciclovir is used in practice, a concentration of 250 mg/mL is preferred over 400 mg/mL given the lower accuracy of the higher concentration.

Oral gel loaded with penciclovir-lavender oil nanoemulsion to enhance bioavailability and alleviate pain associated with herpes labialis.

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.

Prediction of Kidney Drug Clearance: A Comparison of Tubular Secretory Clearance and Glomerular Filtration Rate.

BACKGROUND: Although proximal tubular secretion is the primary mechanism of kidney drug elimination, current kidney drug dosing strategies are on the basis of eGFR. METHODS: In a dedicated pharmacokinetic study to compare GFR with tubular secretory clearance for predicting kidney drug elimination, we evaluated stable outpatients with eGFRs ranging from 21 to 140 ml/min per 1.73 m2. After administering single doses of furosemide and famciclovir (metabolized to penciclovir), we calculated their kidney clearances on the basis of sequential plasma and timed urine measurements. Concomitantly, we quantified eight endogenous secretory solutes in plasma and urine using liquid chromatography-tandem mass spectrometry and measured GFR by iohexol clearance (iGFR). We computed a summary secretion score as the scaled average of the secretory solute clearances. RESULTS: Median iGFR of the 54 participants was 73 ml/min per 1.73 m2. The kidney furosemide clearance correlated with iGFR (r=0.84) and the summary secretion score (r=0.86). The mean proportionate error (MPE) between iGFR-predicted and measured furosemide clearance was 30.0%. The lowest MPE was observed for the summary secretion score (24.1%); MPEs for individual secretory solutes ranged from 27.3% to 48.0%. These predictive errors were statistically indistinguishable. Penciclovir kidney clearance was correlated with iGFR (r=0.83) and with the summary secretion score (r=0.91), with similar predictive accuracy of iGFR and secretory clearances. Combining iGFR with the summary secretion score yielded only modest improvements in the prediction of the kidney clearance of furosemide and penciclovir. CONCLUSIONS: Secretory solute clearance measurements can predict kidney drug clearances. However, tight linkage between GFR and proximal tubular secretory clearance in stable outpatients provides some reassurance that GFR, even when estimated, is a useful surrogate for predicting secretory drug clearances in such patients.

Modifications on the heterocyclic base of ganciclovir, penciclovir, acyclovir - syntheses and antiviral properties.

АBSTRACTEsters of the antiherpetic drugs ganciclovir, penciclovir with the bile acids (cholic, chenodeoxycholic and deoxycholic) and amino acid esters of acyclovir were generated and evaluated for their in vitro antiviral activity against herpes simplex viruses type 1 and type 2 (HSV-1, HSV-2). The antiviral assays demonstrated that modified analogs of ACV and PCV are less active compared to the initial substances against HSV-1and HSV-2. CC50 for ganciclovir-deoxycholate corresponded to the CC50 of the other analogs and its activity is lower than ganciclovir. Obtained results show that tested modification do not improve bioavailability of nucleoside analogs in cells.

Solid-State Characterization and Compatibility Studies of Penciclovir, Lysine Hydrochloride, and Pharmaceutical Excipients.

The physical and chemical characterization of the solid-state properties of drugs and excipients is fundamental for planning new formulations and developing new strategies for the treatment of diseases. Techniques such as differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy are among the most commonly used techniques for these purposes. Penciclovir and lysine are individually used to treat the herpes virus. As such, the development of a formulation containing both drugs may have therapeutic potential. Solid-state characterization showed that both penciclovir and lysine were crystalline materials with melting points at 278.27 °C and 260.91 °C, respectively. Compatibility studies of penciclovir and lysine indicated a possible interaction between these substances, as evidenced by a single melting point at 253.10 °C. The compatibility of several excipients, including ethylenediaminetetraacetic acid, cetostearyl alcohol, sodium lauryl sulphate, di-tert-butyl methyl phenol, liquid petrolatum, methylparaben, nonionic wax, paraffin, propylene glycol, and propylparaben, was evaluated in ternary (penciclovir-lysine-excipient) mixtures (1:1:1, w/w/w) to determine the optimal formulation. The developed formulation was stable under accelerated and ambient conditions, which demonstrated that the interaction between penciclovir and lysine was suitable for the development of a formulation containing both drugs.

Synthesis and anti-HSV activity of tricyclic penciclovir and hydroxybutylguanine derivatives.

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-C6H4) displayed good inhibitory activity (HSV-1 EC50 1.5 µM, HSV-2 EC50 0.8 µM) and retained inhibitory activity in HSV-1 TK- cells (EC50 0.8 µM). Computational docking experiments supported the biological data observed and this preliminary study provides useful data for further development of tricyclic acyclic nucleoside derivatives with improved lipophilicity and retention of activity in HSV-1 TK deficient strains. Also, the new tricyclic derivatives were evaluated against a broad range of other DNA and RNA viruses, but were found to be inactive at subtoxic concentrations. In addition, weak to moderate cytostatic effect was observed for the new compounds.

Pilot Study of the Safety and Tolerability of a Subconjunctival Penciclovir Implant in Cats Experimentally Infected with Herpesvirus.

PURPOSE: To assess safety and tolerability of a subconjunctival penciclovir implant in cats infected with feline herpesvirus type 1 (FHV-1). METHODS: Subconjunctival blank (n = 4 cats) or penciclovir-impregnated (n = 6) silicone implants were placed bilaterally in 10 normal, FHV-1-naive cats 7-8 days before viral inoculation. Outcomes included disease score, FHV-1 serology, conjunctival viral load, Schirmer tear tests (STT), tear film break-up times (TFBUTs), conjunctival histology, goblet cell density (GCD), body weight, tear and plasma penciclovir concentration, and corneal ulcer evaluation. RESULTS: Both groups had similar clinical and histologic disease scores, STT values, TFBUTs, GCD, FHV-1 titers, viral loads, and body weight changes. No ocular or systemic signs of toxicity were noted. Tear penciclovir concentration varied widely among cats and across time points. Tear penciclovir concentrations exceeded the lowest published half maximal inhibitory concentration (IC50) in 5/6 treated cats. Plasma penciclovir concentrations remained below 10 ng/mL. Cats with higher tear penciclovir concentrations at inoculation and/or time of peak disease had fewer corneal ulcers than cats in which tear penciclovir concentrations were inconsistent, low, or unrecordable. CONCLUSIONS: Subconjunctival blank and penciclovir-impregnated implants were well tolerated at the ocular surface and not associated with systemic toxicity, adverse effect, or appreciable plasma penciclovir concentrations. Tear penciclovir concentrations >IC50 were sometimes achieved, especially during burst release soon after implant placement. Further study is necessary to determine efficacy of locally delivered penciclovir when penciclovir concentration is consistently maintained above IC50. This will be especially useful in patients unable to receive systemic therapy.

Prophylactic and therapeutic effects of twice-daily famciclovir administration on infectious upper respiratory disease in shelter-housed cats.

OBJECTIVES: In humans with herpetic disease, early or pre-emptive famciclovir therapy reduces disease duration and severity. This prospective, masked, placebo-controlled study tested therapeutic and prophylactic effects of two famciclovir doses given to cats for 7 days following shelter entry. METHODS: Cats were assigned to prophylactic or therapeutic study arms based on clinical evidence of herpetic disease at study entry. Cats in the therapeutic arm received no treatment (n = 19), placebo (lactose; n = 18) or famciclovir at ~30 (n = 21) or ~90 mg/kg (n = 20) PO q12h for 7 days. Cats in the prophylactic arm received no treatment (n = 25) or famciclovir at ~30 (n = 28) or ~90 mg/kg (n = 27) PO q12h for 7 days. Disease scores, body weight, conjunctival feline herpesvirus 1 (FHV-1) shedding, and adoption rates were recorded on days 1 (admission), 8 (end of therapy) and 15 (1 week after cessation of therapy). RESULTS: No significant differences in clinical scores were observed among groups in the prophylactic or therapeutic arms at any of the three time points. However, within the therapeutic arm, viral shedding on day 8 was significantly higher in cats receiving no treatment than in those receiving ~30 or ~90 mg/kg famciclovir, and this effect persisted 1 week after famciclovir was stopped (day 15) only in cats receiving ~30 mg/kg, although this approached significance in cats receiving ~90 mg/kg. No significant differences in adoption rates were detected among groups in either arm throughout the study. CONCLUSIONS AND RELEVANCE: Although we did not demonstrate a statistically or clinically significant effect of famciclovir administration upon clinical signs of infectious upper respiratory disease or adoption, when it was administered at ~30 or ~90 mg/kg q12h for 1 week famciclovir reduced conjunctival FHV-1 shedding. This suggests a potential role in interrupting the infectious cycle within a shelter population; however, cost in time and resources, and stress and pathogen transmission induced by oral administration should be considered.

In vitro studies with two human organic anion transporters: OAT2 and OAT7.

1. Penciclovir, ganciclovir, creatinine, para-aminohippuric acid (PAH), ketoprofen, estrone 3-O-sulfate (E3S), dehydroepiandrosterone 3-O-sulfate (DHEAS) and cyclic guanosine monophosphate (cGMP) were screened as substrates of human liver organic anion transporters OAT2 and OAT7. 2. For OAT7, high uptake ratios (versus mock transfected HEK293 cells) of 29.6 and 15.3 were obtained with E3S and DHEAS. Less robust uptake ratios (≤3.6) were evident with the other substrates. OAT2 (transcript variant 1, OAT2-tv1) presented high uptake ratios of 30, 13, ∼35, ∼25, 8.5 and 9 with cGMP, PAH, penciclovir, ganciclovir, creatinine and E3S, respectively. No uptake was observed with DHEAS. 3. Although not a substrate of either transporter, ketoprofen did inhibit transfected OAT2-tv1 (IC50 of 17, 22, 23, 24, 35 and 586 µM; creatinine, ganciclovir, penciclovir, cGMP, E3S and prostaglandin F2α, respectively) and penciclovir uptake (IC50 = 27 µM; >90% inhibition) by plated human hepatocytes (PHH). 4. It is concluded that penciclovir and ketoprofen may serve as useful tools for the assessment of OAT2 activity in PHH. However, measurement of OAT7 activity therein will prove more challenging, as high uptake rates are evident with E3S and DHEAS only and both sulfoconjugates are known to be substrates of organic anion transporting polypeptides.

Biophysical and In Silico Studies of the Interaction between the Anti-Viral Agents Acyclovir and Penciclovir, and Human Serum Albumin.

Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus infections. In the present research their binding properties with human serum albumin (HSA) were studied using different advanced spectroscopic and in-silico methods. The interactions between ACV/PNV and HSA at the three investigated temperatures revealed a static type of binding. Extraction of the thermodynamic parameters of the ACV-HSA and PNV-HSA systems from the measured spectrofluorimetric data demonstrated spontaneous interactions with an enthalpy change (∆H°) of -1.79 ± 0.29 and -4.47 ± 0.51 kJ·mol-1 for ACV and PNV, respectively. The entropy change (∆S°) of 79.40 ± 0.95 and 69.95 ± 1.69 J·mol-1·K-1 for ACV and PNV, respectively, hence supported a potential contribution of electrostatic binding forces to the ACV-HSA and PNV-HSA systems. Putative binding of ACV/PNV to HSA, using previously reported site markers, showed that ACV/PNV were bound to HSA within subdomains IIA and IIIA (Sudlow sites I and II). Further confirmation was obtained through molecular docking studies of ACV-HSA and PNV-HSA binding, which confirmed the binding site of ACV/PNV with the most stable configurations of ACV/PNV within the HSA. These ACV/PNV conformers were shown to have free energies of -25.61 and -22.01 kJ·mol-1 for ACV within the HSA sites I and II and -22.97 and -26.53 kJ·mol-1 for PNV in HSA sites I and II, with hydrogen bonding and electrostatic forces being the main binding forces in such conformers.

Herpes Labialis: An Update.

BACKGROUND: Herpes labialis is characterized by recurrent vesicular eruptions primarily on the lips and perioral skin. The condition is contagious, can cause significant discomfort/pain, and can have an adverse effect on the quality of life. OBJECTIVE: To update the evaluation and treatment of herpes labialis. METHODS: A PubMed search was completed in Clinical Queries using the key term "herpes labialis". Patents were searched using the key term "herpes labialis" from www.freepatentsonline.com. RESULTS: The diagnosis of herpes labialis is mainly clinical based on classic grouped lesions (papules, vesicles, ulcers) on the lip. Antiviral therapy shortens the duration of pain and discomfort, hastens healing, and reduces viral shedding. Thus, episodic treatment is warranted, especially if the patient desires treatment for cosmetic purposes or for relief of pain. Such treatment needs to be initiated promptly, ideally in the prodromal stage and no later than 48 hours from the onset of lesions to achieve optimal results. Chronic suppressive therapy with oral antiviral agents should be considered for patients with severe or frequent (six or more episodes per year) recurrences. Recent patents related to the management of herpes labialis are also discussed. CONCLUSION: For episodic treatment, oral antiviral agents, such as acyclovir (Zovirax), valacyclovir (Valtrex) and famciclovir (Famvir), are superior to topical antiviral therapy. Valacyclovir and famciclovir have greater oral bioavailability and are better absorbed than acyclovir, require less frequent dosing, but are more expensive and are not approved for children. Topical antiviral agents such as 5% acyclovir cream/ointment (Zovirax) ± hydrocortisone (Xerese), 1% penciclovir (Denavir) cream, and 50 mg Buccal Adhesive Tablet (ABT-50 mg) can also be used for episodic treatment of herpes labialis. These topical agents are not effective in the prevention of recurrent herpes labialis. For chronic daily suppressive therapy, oral antivirals are the treatment of choice.

Retrospective analysis of penciclovir combined with foscarnet sodium in the treatment of herpes zoster / 中华实验和临床病毒学杂志

Objective@#To evaluate the therapeutic efficacy of penciclovir combined with foscarnet sodium in the treatment of herpes zoster.@*Methods@#The clinical datas of 135 herpes zoster patients from the ward of Department of Dermatology, Tianjin Medical University General Hospital were collected. Among them 64 patients received penciclovir and foscarnet sodium, and the remaining 71 patients only received penciclovir alone.Their general information, the time for vesicle stopped emerging, rash began to scab, pain to relief obviously, the adverse reaction and if they got the postherpetic neuralgia were recorded and included into statistical analysis.@*Results@#The general information showed no significant differences between the 2 groups(all P>0.05). The time for vesicle stopped emerging, rash began to scab, pain to relief obviously in combination group was shorter than the penciclovir group (all P<0.001). The number of patients who developed postherpetic neuralgia of combination group was fewer than that of penciclovir group(P=0.013). There was no statistical significance between the 2 groups the adverse reaction(P=0.928).@*Conclusions@#The penciclovir and foscarnet sodium combination therapy showed rapid therapeutic effects on herpes zoster patients, the incidence of postherpetic neuralgia was low, and there was no more side effects than penciclovir alone therapy. The combined therapy may be a reliable way to treat herpes zoster.

Effects of four nucleoside analogues used as antiviral agents on rat Sertoli cells (SerW3) in vitro.

Some nucleoside analogues are used to treat herpes simplex and other viral infections. They are known to impair spermatogenesis, but published data are scarce. We studied the effects of four nucleosides on SerW3 cells, a rat Sertoli cell line. Cells were cultured for 3 days in DMEM supplemented with four different concentrations of each drug. Aciclovir and ganciclovir were added at concentrations of 0.3, 1, 3 and 10 mg/l medium; penciclovir and its prodrug famciclovir were used at higher concentrations (3, 10, 30, 100 mg/l medium). After a culture period of 3 days, we analysed the expression of connexin43, N-cadherin and the cytoskeleton protein vimentin by Western blot. Aciclovir caused a clear-cut effect at the highest concentration tested (10 mg/l), which is less than the peak plasma concentration achieved in patients during intravenous therapy with the drug. Connexin43, vimentin and N-cadherin content decreased to 49.8 ± 17, 44.0 ± 4 and 75.4 ± 1.5 % of the control values, respectively (n = 3; mean ± SD). Similar effects were observed with the prodrug ganciclovir (43.2 ± 10.8; 54.1 ± 11.9; 84.4 ± 10.8 % of controls). Penciclovir caused less pronounced effects at 10 mg/l medium (82.1 ± 20.6; 90.0 ± 12.0; 76.5 ± 17.7 % of controls). Only a slight effect was observed with famciclovir. Even at a 10-fold concentration (100 mg/l), just moderate changes were induced. In summary, we observed clear-cut effects with aciclovir and ganciclovir on Sertoli cells in vitro at therapeutically relevant concentrations and identified connexin43 as the most sensitive marker.

Clinical and antiviral effect of a single oral dose of famciclovir administered to cats at intake to a shelter.

Although famciclovir is efficacious in feline herpesvirus type 1 (FHV-1)-infected cats, effects of a single dose early in disease course have not been reported. In this two part, randomized, masked, placebo controlled study, cats received a single dose of 125 mg famciclovir (n = 43) or placebo (n = 43; pilot study), or 500 mg famciclovir (n = 41) or placebo (n = 40; clinical trial) on entering a shelter. FHV-1 PCR testing was performed, bodyweight and food intake were recorded, and signs of respiratory disease were scored prior to and 7 days following treatment. FHV-1 DNA was detected in 40% of cats in both parts at study entry. In the pilot study, ocular and nasal discharge scores increased from days 1 to 7 in famciclovir and placebo treated cats. Sneezing scores increased and bodyweight decreased in famciclovir-treated cats. The proportion of cats in which FHV-1 DNA was detected increased over time in all cats in the pilot study. In the clinical trial, food intake and median clinical disease scores for nasal discharge and sneezing increased from days 1 to 7 in both groups and demeanor scores worsened in famciclovir-treated cats. The proportion of cats shedding FHV-1 DNA was greater on day 7 than on day 1 in cats receiving 500 mg famciclovir. A single dose of famciclovir (125 or 500 mg) administered at shelter intake was not efficacious in a feline population in which 40% were already shedding FHV-1.