Oral Administration Of Acyclovir Research Articles

Herpes Zoster Infection in A Case of Nephrotic Syndrome (On Alternate Day Prednisolone Therapy) - A Case Report

Herpes Zoster infection is caused by Varicella Zoster virus. Its characteristic feature is the appearance of unilateral clustered vesicles on an erythematous base. The vesicles heals within two weeks from appearance of vesicles. The symptoms of Nephrotic Syndrome include severe proteinuria, edema, hypoalbuminemia and hyperlipidemia. Minimal Change Nephrotic Syndrome is the most prevalent type of nephrotic syndrome in children, for which prednisolone is the preferred medication. Administration of prolonged corticosteroid causes decreased cell mediated immunity which causes immunosuppression and therefore chance of infection increases. Herpes zoster infection is usually a self-limiting disease. It is usually diagnosed clinically on the basis of characteristic appearance of the rash. Treatment is mainly by administration of oral acyclovir for 7 days. Severe illness may require hospitalization for intravenous acyclovir. In individuals with nephrotic syndrome on corticosteroids or other immunosuppressive medications, complication arising from varicella infections can be life-threatening. Keywords: Herpes zoster, Nephrotic syndrome, Minimal Change Nephrotic Syndrome, Prednisolone, Acyclovir, Cell mediated immunity

Valaciclovir: Its Antiviral Activity, Pharmacokinetic Properties and Therapeutic Efficacy in Herpesvirus Infections: An Review

Valaciclovir, the L-valyl ester of aciclovir (acyclovir), is an oral prodrug that undergoes rapid and extensive first-pass metabolism to yield aciclovir and the essential amino acid L-valine. Aciclovir, the active antiviral component of valaciclovir, shows good in vitro activity against the herpesviruses herpes simplex virus (HSV)-1, HSV-2 and varicella zoster virus. The bio availability of aciclovir from oral valaciclovir is considerably greater than that achieved after oral acyclovir administration. Valaciclovir is an effective treatment for herpes zoster in immunocompetent adults. Valaciclovir was also effective in suppressing recurrent episodes of genital herpes and significantly prolonged the time to a recurrent episode of infection compared with placebo

Enhanced Transdermal Delivery of Acyclovir via Hydrogel Microneedle Arrays

Hydrogel microneedles represent a promising approach to deliver drug molecules across skin into systemic circulation in a sustained release manner and without any polymer residue within skin. Acyclovir is an antiviral drug used for the treatment of several viral infections. However, the oral administration of acyclovir may cause gastrointestinal tract (GIT) disturbances with low bioavailability and poor patient compliance due to its requirement of five daily administrations to produce the desired effect. Therefore, it is thought that the preparation of hydrogel microneedle arrays containing acyclovir would improve the bioavailability and patient compliance by reducing the frequency of administration to once daily as well as overcome the GIT side effects associated with oral administration. A mixture of PEG 10,000 Da and PMVE/MA co-polymer 1,980,000 Da at a ratio of 1:3 (7.5%:22.5% w/w) with Na2CO3 3% w/w was found to produce the optimum hydrogel microneedle array formulation (F8) which showed suitable needle formation with an appropriate mechanical strength and excellent insertion ability, high drug content, sufficient swelling property and a sustained drug release over a period of 24 hours. The Ex vivo permeation study across human skin has demonstrated that the permeation of acyclovir from F8 hydrogel microneedle array was significantly (P≤ 0.05) increased by 39 times in comparison with microneedle-free film (control). The microneedle array has delivered 75.56% ± 4.2 of its loading dose over 24 hours, while the control film was only able to deliver 1.94% ± 0.14 of the total loading dose during the same period. Accordingly, these findings propose the potential application of hydrogel microneedle arrays for the transdermal delivery of acyclovir in a sustained release manner over 24 hours.

Parameterization of small intestinal water volume using PBPK modeling

To facilitate accurate predictions of oral drug disposition, mechanistic absorption models require optimal parameterization. Furthermore, parameters should maintain a biological basis to establish confidence in model predictions. This study will serve to calculate an optimal parameter value for small intestinal water volume (SIWV) using a model-based approach. To evaluate physiologic fidelity, derived volume estimates will be compared to experimentally-based SIWV determinations. A compartmental absorption and transit (CAT) model, created in Matlab-Simulink®, was integrated with a whole-body PBPK model, developed in PK-SIM 5.2®, to provide predictions of systemic drug disposition. SIWV within the CAT model was varied between 52.5mL and 420mL. Simulations incorporating specific SIWV values were compared to pharmacokinetic data from compounds exhibiting solubility induced non-proportional changes in absorption using absolute average fold-error. Correspondingly, data pertaining to oral administration of acyclovir and chlorothiazide were utilized to derive estimates of SIWV. At 400mg, a SIWV of 116mL provided the best estimates of acyclovir plasma concentrations. A similar SIWV was found to best depict the urinary excretion pattern of chlorothiazide at a dose of 100mg. In comparison, experimentally-based estimates of SIWV within adults denote a central tendency between 86 and 167mL. The derived SIWV (116mL) represents the optimal parameter value within the context of the developed CAT model. This result demonstrates the biological basis of the widely utilized CAT model as in vivo SIWV determinations correspond with model-based estimates.

Dexamethasone as adjunctive therapy for treatment of varicella pneumonia

BackgroundThe most common and most serious complication of varicella (chickenpox) in adults is pneumonia, which can lead to severe respiratory failure. Whether addition of corticosteroids to antiviral treatment benefits patients with varicella pneumonia is unclear. ObjectivesTo assess the effect of dexamethasone as adjunctive therapy for treatment of varicella pneumonia on the length of hospital stay, which might cause earlier resolution of varicella pneumonia. Patients and methodsForty patients were diagnosed as varicella pneumonia and divided into two groups, the first one involved 20 patients who received dexamethasone and acyclovir, and the second one involved also 20 patients but they received placebo and acyclovir. We measured liver function test, kidney profile, complete blood count, blood glucose, C-reactive protein and the levels of interleukin-6 on the day of presentation, after 4days of admission and on the day of discharge from the hospital. ResultThe mean length of hospital stay in the dexamethasone group was 6.5days compared with 7.1days in the placebo group and was significantly different between two groups. The mean time of switching to oral administration of acyclovir was 3.4days in the dexamethasone group and 4.2days in the placebo group. The mean time of switching to oral was significantly lower in dexamethasone group than in placebo group. ConclusionAdding of dexamethasone to acyclovir in patients with varicella pneumonia can reduce the length of hospital stay.

Bullous Cutaneous Eruption due to Extravasation of Acyclovir in an Adolescent with Acute Lymphoblastic Leukemia.

A 14-year-old-girl undergoing treatment with the BFMTRALL 2000 protocol (MRG ) because of early pre-B-cellacute lymphoblastic leukemia (ALL ) developed chickenpox on the 33rd d of remission induction. As such, chemotherapywas withdrawn and the patient was quarantined.Acyclovir (1500 mg·m–2·d–1 in three divided doses)was then administered in 100 mL of 0.9% sodium chloride,as 1-h intravenous infusions. On the 9th d of acyclovirtherapy 10 min after infusion of the 27th dose startedthe patient complained of the sensation of minor pain andburning in the region of Intracath catheter insertion, anddeveloped slight erythema with irregular boundaries inthe same region. The infusion line was checked for patency by gentlywithdrawing blood before, which showed that the linewas patent, and then infusion was continued, but at aslower rate. The line’s patency was checked frequently andremained patent. The patient no longer experienced thesensation of pain and burning, and the erythema improvedslightly; however, at the end of the infusion (the 65th min)a solitary, bullous painless eruption 1 x 1 cm in diameterwas observed on the tract of the vein, 10 cm distal of theIntracath insertion (Figures ​(Figures11,​,22,3,4). Without any medicalintervention the lesion subsided in 8 h and disappearedcompletely in 24 h, leaving behind a residual scar lesion. Figure 1 Cutaneous vesicular eruption on the forearm ofthe patient which developed after acyclovir injection. Figure 2 Cutaneous vesicular eruption on the forearm ofthe patient which developed after acyclovir injection. Figure 3 Cutaneous vesicular eruption on the forearm ofthe patient which developed after acyclovir injection. The known adverse dermatological effects of acyclovir,including erythema, inflammation, and phlebitis at the siteof intravenous infusion, occur in ≤16% of patients, presumablydue to the alkaline nature of the solution (reconstitutedacyclovir has a pH of 10-11) [1]. It is a knownirritant to venous and soft tissue if extravasated [2].Wethink that both the erythema and bullous eruption inthe presented case were signs of subcutaneous acyclovirextravasation, despite the fact that we frequently checkedthe line and were confident of its patency. Frequent venipuncture of the same veins and use ofchemotherapeutic agents in oncology patients may rendertheir veins fragile and susceptible to the irritant effects ofdrugs. As such, sensation of pain and burning in oncologypatients should be considered a reliable sign of extravasationeven when good blood return is observed. Nonetheless,cutaneous vesicular eruption following intravenousacyclovir administration is rare [1]. It was reported thatcutaneous vesicular eruptions developed not only at thesite of injection, but far from it [3] and proximal to it [1].Moreover, bullous eruptions were also reported followingtopical and oral acyclovir administration [1]; therefore,rather than extravasation of acyclovir solution, an immunoallergicpattern in the presence of histological leukocytoclasticvasculitis is an etiological consideration [3]. The presented case shows that the irritant effects ofacyclovir should always be a consideration, especially inoncology patients, and that the development of new vesiculareruptions during acyclovir therapy should not alwaysbe considered progression of herpes infection. Conflict of Interest Statement The authors of this paper have no conflicts of interest,including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materialsincluded. Acknowledgement I thank Lale Olcay, MD for kindly revising the manuscript.

Effect of Age on the Gastrointestinal Absorption of Acyclovir in Rats

Drug elimination from the body after intravenous administration of acyclovir (20 mg kg-1) was delayed in 1-week-old rats but the pharmacokinetic data for 2.5-week-old rats were the same as those for 8-week-old rats. The areas under the plasma concentration-time curves at 0-infinity h (AUC) after oral administration of acyclovir (20 mg kg-1) decreased with increasing age. The absolute bioavailabilities for 1-, 2.5-, 3- and 8-week-old rats were 77.59, 51.52, 14.61 and 7.30%, respectively. The gastrointestinal absorption of poorly absorbed acyclovir was good for rats younger than 2.5 weeks but dropped abruptly between 2.5 and 3 weeks of age. The intestinal membrane permeability of acyclovir was studied using the everted sac method. The rate of transfer of an initial concentration of 10 microM acyclovir from the mucosal to the serosal side was constant until 60 min in rats of different ages while the rate in 2.5-week-old rats was significantly greater than that in 3-, 4- and 8-week-old rats. Abrupt in-vivo and in-vitro changes were observed in the experimental results between 2.5- and 3-week-old rats; this period coincided with the weaning period of the rat. The membrane transport mechanism of acyclovir in 2.5- and 8-week-old rats was also studied. Cumulative transferred amounts of acyclovir were linear (r = 0.99) over the range 5 microM-1 mM and dose-independent. The influence of metabolic inhibitors (sodium azide, 2,4-dinitrophenol, ouabain), purine and pyrimidine analogues (2-deoxyguanosine, guanine, adenine, uridine) and temperature on the permeation of acyclovir was studied. The permeation of acyclovir was inhibited only by 2-deoxyguanosine and guanine in 2.5-week-old rats. These results suggest that throughout the maturation period, the gastrointestinal absorption mechanism of acyclovir is predominantly via passive diffusion with little or no active or facilitated transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Disposition kinetics of a dipeptide ester prodrug of acyclovir and its metabolites following intravenous and oral administrations in rat

The objective of this work was to study the disposition kinetics of valine-valine-acyclovir (VVACV), a dipeptide ester prodrug of acyclovir following intravenous and oral administrations in rat. A validated LC-MS/MS analytical method was developed for the analysis VVACV, Valine-Acyclovir (VACV), and Acyclovir (ACV) using a linear Ion Trap Quadrupole. ACV was administered orally for comparison purpose. In the VVACV group, both blood and urine samples and in the ACV group only blood samples were collected. All the samples were analyzed using LC-MS/MS. The LLOQ for ACV, VACV, and VVACV were 10, 10, and 50 ng/ml, respectively. Relevant pharmacokinetic parameters were obtained by non-compartmental analyses of data with WinNonlin. Following i.v. administration of VVACV, AUC(0-inf) (min*µM) values for VVACV, VACV, and ACV were 55.06, 106, and 466.96, respectively. The AUC obtained after oral administration of ACV was 178.8. However, following oral administration of VVACV, AUC(0-inf) values for VACV and ACV were 89.28 and 810.77, respectively. Thus the exposure of ACV obtained following oral administration of VVACV was almost 6-fold higher than ACV. This preclinical pharmacokinetic data revealed that VVACV has certainly improved the oral bioavailability of ACV and is an effective prodrug for oral delivery of ACV.

Recurrent lumbosacral herpes simplex in two men

Two cases of recurrent lumbosacral herpes simplex without concomitant genital lesions are reported. Both patients presented with vesicular lesions on the middle of the lower back and on the left...

Relationships Between Late Viral Infections and Immune Reconstitution after Hematopoietic Stem Cell Transplantation.

Late occurrence of viral infections beyond day 100 after hematopoietic stem cell transplantation (HSCT) was widely recognized to depend on the profound immune suppression due to severe chronic GVHD and its treatment. However, there have been few reports clarifying the direct relationships between the development of late viral infections and immune reconstitution after HSCT. To evaluate the correlation of the immune recovery with the occurrence of late cytomegalovirus (CMV) or varicella-zoster virus (VZV) infections, we retrospectively analyzed the records of 60 Japanese adult patients who underwent allogeneic HSCT for the first time from April, 2002 to February, 2007 at the University of Tokyo Hospital, and survived longer than 180 days after HSCT. Absolute lymphocyte subset counts (CD3+ T cells, CD3−CD19+ B cells, CD3+CD4+ helper T cells, CD4+CD45RO+ memory T cells, CD4+CD45RA+ naïve T cells, CD3+CD8+ cytotoxic T cells, CD3−CD56+ natural killer cells), absolute monocyte counts, serum IgG, IgA, and IgM levels were measured at 3 and 6 months after HSCT. As a prophylaxis against late CMV disease, risk-adopted preemptive therapy with ganciclovir was performed by monitoring CMV antigenemia beyond day 100 after HSCT. For late VZV disease, oral administration of acyclovir at 200 mg/day was principally continued until the end of immunosuppressive therapy and at least one year after HSCT in 52 patients, whereas valacyclovir at 500 mg/day three times a week was administered until one year after HSCT in eight patients. Two out of 60 patients have already developed CMV disease within 100 days after HSCT. Thirteen of the remaining 58 patients developed late CMV infection defined as 10 or more CMV-Ag positive cells per two slides at a median of 125 days (101 to 546 days) after HSCT. CD3+ T cells less than 400x106/L (P=0.003), CD3+CD4+ T cells less than 200 x106/L (P=0.013), CD4+CD45RO+ T cells less than 100x106/L (P<0.001), CD4+CD45RA+ T cells less than 50x106/L (P<0.001), and CD3+CD8+ T cells less than 400x106/L (P=0.005) at 3 months after HSCT were associated with a high incidence of late CMV infections. Of these, six patients developed high-grade CMV antigenemia with 50 or more positive cells, for which CD4+CD45RO+ T cells less than 100x106/L (P=0.043) was the only significant risk factor. Nine of the 58 patients developed late CMV disease (retinitis in 7 and colitis in 2) at a median of 160 days (114 to 215 days) after HSCT. CD3+CD4+cell less than 300 x106/L (P=0.047) and CD4+CD45RA+ less than 50 x106/L (P=0.043) were identified as risk factors for the CMV disease, and CD3+CD4+cell counts were less than 300x106/L in all of the nine patients (median of 75 x106/L, range 12 to 273 x106/L). None developed VZV disease within 100 days after HSCT, while eleven of the 60 patients developed late VZV disease later on, a median of 481 days (149 to 1034 days) after HSCT. CD4/CD8 ratio less than 0.4 at 3 months after HSCT was the only significant risk factor for late VZV disease (P=0.043), whereas the absolute CD3+CD4+ cell count was similar and CD3+CD8+ cell count was rather higher in patients who developed VZV disease compared to those who did not. Among 35 patients who received anti-VZV prophylaxis at least 6 months after HSCT and discontinued thereafter, nine developed late VZV disease after day 180, in all of whom CD4/CD8 ratio at 6 months was less than 0.5 (median 0.18, range 0.11 to 0.42). Two patients showed cutaneous dissemination at day 481 and day 571 after HSCT, whose CD4/CD8 ratio was 0.16 or 0.22 at 3 months, and 0.25 or 0.17 at 6 month after HSCT, respectively. These finding suggested that the development of late CMV infection and disease was associated with a low CD3+CD4+ T cell count, whereas late VZV disease tended to occur in patients with a low CD4/CD8 ratio. Patients with enough CD3+CD8+ cells but with insufficient CD3+CD4+ cells, probably due to the resumed immunosuppressants, might be at highest risk for VZV disease.

Pharmacokinetics of Acyclovir after Intravenous Infusion of Acyclovir and after Oral Administration of Acyclovir and Its Prodrug Valacyclovir in Healthy Adult Horses

The purpose of this study was twofold. The first aim was to evaluate the oral bioavailability and pharmacokinetics (PKs) of acyclovir in horses after intravenous (i.v.) administration and after oral administration of acyclovir and its prodrug, valacyclovir. Second, we aimed to combine these PK data with pharmacodynamic (PD) information, i.e., 50% effective concentrations (EC(50) values) from in vitro studies, to design an optimal dosage schedule. Three treatments were administered to healthy adult horses: 10 mg of acyclovir/kg of body weight delivered as an i.v. infusion over 1 h, 20 mg of acyclovir/kg administered as tablets by nasogastric intubation, and 20 mg of valacyclovir/kg administered as tablets by nasogastric intubation. Total plasma concentrations were measured by a high-performance liquid chromatography method combined with fluorescence detection, while unbound plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. The peak concentration of i.v. acyclovir was approximately 10 mug/ml for both the total and the unbound plasma concentrations. The mean half-life of elimination was between 5.05 h (total concentration) and 11.9 h (unbound concentration). Oral administration of acyclovir resulted in low maximum concentration in plasma (C(max)) and poor bioavailability. A 10-times-higher C(max) and an 8-times-higher bioavailability were achieved with oral administration of valacyclovir. The i.v. administration of 10 mg/kg acyclovir and the oral administration of 20 mg/kg valacyclovir achieved concentrations within the sensitivity range of equine herpesvirus type 1 (EHV-1). The higher bioavailability of valacyclovir makes it an attractive candidate for the prophylactic and/or therapeutic treatment of horses infected with EHV-1. The results from the PK/PD modeling showed that a dosage of 40 mg/kg valacyclovir, administered three times daily, would be sufficient to reach plasma concentrations above the EC(50) values.

Clinical Analysis of Herpetic Keratitis in Korea

Purpose: To investigate the clinical characteristics of herpetic keratitis in Korea. Methods: A retrospective analysis was performed on 90 eyes of 84 patients who were clinically diagnosed with herpetic keratitis and were followed for at least 4 months or more. Information on prior herpetic keratitis, type of keratitis, time to remission, recurrence rate, administration of oral acyclovir, final visual acuity was reviewed. Remission time and recurrence rate were compared according to types of herpetic keratitis and the application of oral acyclovir in epithelial, stromal or endothelial keratitis; and the relation of history of previous herpetic keratitis, recurrence and final vision, was analyzed. Results: Sex ratio (M:F) was 1.31 and the mean age was 54.6 years. Of 90 eyes, the proportion of infectious epithelial keratitis, stromal keratitis, endothelitis and neurotrophic ulcer was 51.1, 17.8, 25.6 and 5.6%, respectively. The mean remission time was 1.92±1.01, 4.13±5.05, 5.52±5.08, 4.00±1.00, respectively (p=0.001, one-way Anova). Recurrence occurred in 21 (42.9%) eyes of 49, which were followed up for more than 12 months, in a year after the previous attack. The rates of recurrence of infectious epithelial keratitis, stromal keratitis and endothelitis were 25.0%, 63.6% and 53.8%, respectively. Oral acyclovir neither shortens the remission nor prevents the recurrence. The percentage of final vision over 20/40 in infectious epithelial keratitis, stromal keratitis and endothelitis was 81.1, 57.1 and 60.0%, respectively. The final vision was worse in the group with a history of herpetic keratitis. Conclusions: Stromal keratitis and endothelitis showed a higher recurrence rate and longer remission time than infectious epithelial keratitis. Because recurrent and severe keratitis may result in corneal opacity and vision loss, aggressive and proper treatment is needed. However, these cases are often resistant to therapy.

Pharmacokinetics of Acyclovir after Single Intravenous and Oral Administration to Adult Horses

The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.

Effect of acyclovir on thermal stress–induced herpesvirus reactivation

Purpose. Acyclovir has been shown to be effective in preventing recurrent herpes simplex virus lesions of the genitalia and oral labia. The purpose of the current study was to determine the effect of acyclovir on the appearance of infectious virus in the peripheral nervous system and in an end organ, the eye.Materials and methods. Mice latent for the McKrae strain of herpes simplex virus type 1 were given 3.5 mg/ml acyclovir in their drinking water. Control animals received water without drug. Acyclovir treatment was continued for 4 successive days. On the third day, the mice were subjected to a brief period of hyperthermic stress to induce viral reactivation. Twenty-four hours after stress induction, swabs of the ocular surface and homogenates of the cornea and trigeminal ganglia were analyzed for the presence of infectious herpes simplex virus type 1 and viral DNA.Results. Acyclovir treatment significantly decreased the frequency of infectious virus in the ocular tear film and the cornea but not in the trigeminal ganglion. The corneal homogenates of acyclovir-treated animals contained smaller amounts of viral DNA compared with untreated controls, whereas the amounts of viral DNA in the trige-minal ganglia of acyclovir-treated and untreated animals were similar.Conclusions. These results suggest that oral administration of acyclovir, at least at the dose used in this study, is effective in modestly reducing viral replication in peripheral tissues such as the eye but is not effective in inhibiting viral reactivation and viral DNA synthesis in the peripheral nervous system in mice subjected to induction of reactivation by hyperthermic stress.

Spread of varicella-zoster virus DNA to the environment from varicella patients who were treated with oral acyclovir.

The purpose of the present study was to determine the degree of spread of varicella-zoster virus to the environment (VZV) from varicella patients who received oral acyclovir treatment. Over a period of 8 months, seven healthy children (two girls and five boys, 23-64 months of age) with varicella who visited Fujita Health University School of Medicine were treated with routine doses of oral acyclovir (ACV) for 5 days, commencing within 24 h after onset of the disease. Swab samples from the throats of patients and their family members as well as from air purifier filters in their houses were collected for 7 days as frequently as possible after starting treatment for the disease. The VZV DNA in the samples was identified by a sensitive polymerase chain reaction amplification assay. The VZV DNA was detected in 33-100% of throat swab samples from varicella patients by day 7 of the disease, in 17-32% of throat swab samples from family members by day 4 and in 29% of filters from air purifiers by day 3. The results suggest a broad spread of VZV, probably by the airborne route, from the patients with varicella even after the administration of oral ACV.

Varicella exposure in a neonatal medical centre: successful prophylaxis with oral acyclovir

In December 2000, a female infant hospitalized in our Neonatal Care Centre was infected with varicella by her mother. Although prophylactic intravenous acyclovir was administered at a dose of 15 mg/kg daily, she later developed varicella during her hospital stay. We therefore initiated control procedures to prevent further hospital-acquired infections. Oral acyclovir (40 mg/kg daily divided into four doses) was administered prophylactically to six preterm infants in contact with the varicella patient. None of six preterm infants subsequently developed clinical varicella or had any adverse effects associated with acyclovir administration. It is suggested that prophylactic administration of oral acyclovir (40 mg/kg daily) might prevent hospital-acquired varicella-zoster virus (VZV) infections, and that oral acyclovir may be an option for VZV prophylaxis in situations where VZV immunoglobulin is not available.

Determination of acyclovir in plasma by solid-phase extraction and column liquid chromatography.

After oral administration, valacyclovir, the L-valyl ester of acyclovir, converts to the antiherpes virus drug, acyclovir. The bioavailability of acyclovir after valacyclovir administration is between 3- to 4.5-fold higher than that achieved after oral acyclovir administration. Therefore, despite the drug's short terminal half-life (3 hours), acyclovir plasma concentrations obtained after oral administration of the prodrug offer a more convenient dosage regimen in patients with herpes zoster than that required after acyclovir administration. Acyclovir is also used for viral infection prophylaxis in patients with hematologic disorders and in those who have undergone solid organ transplantation. We have described a simple and selective liquid chromatographic method for the determination of acyclovir in plasma using a new polymeric reversed-phase sorbent for solid-phase extraction. A mean acyclovir absolute recovery of 90% was found after elution of the drug from the cartridge with the mobile phase. This procedure allowed us to measure 62.5 ng/mL of acyclovir with an acceptable precision using a plasma volume of 250 microL, and no drug was found to interfere with the assay. This method is suitable for the therapeutic monitoring of acyclovir in patients who have been given a wide variety of coadministered drugs.

Prolonged oral acyclovir administration associated with neutropenia and thrombocytopenia

Prolonged oral acyclovir administration associated with neutropenia and thrombocytopenia

Neonatal herpes simplex virus infections

Neonatal herpes simplex virus (HSV) infection is one of the life-threatening infections of newborns. It affects approximately 1,500 to 2,200 infants per year in the United States. Changes in the presentation of neonatal HSV infection over the past two decades include an increase in the frequency of skin, eye, and mouth (SEM) disease with a relatively unchanged rate of central nervous system (CNS) disease, but a relative decline in disseminated infection. Although the mortality of neonatal HSV infections has declined with current antiviral therapy, the mortality rate in CNS disease (15%) and disseminated disease (57%) remains high. Morbidity has been seen most frequently in infants with CNS and disseminated disease, with seizures or infection with HSV-2 determined to be risk factors for poor outcome in survivors. In a multicenter, randomized, blinded study by the Collaborative Antiviral Study Group, no differences in outcome were seen between neonates treated with vidarabine and acyclovir. More recently, administration of oral acyclovir has been demonstrated to prevent cutaneous recurrences of HSV after neonatal SEM disease. Although promising, this investigational protocol requires further evaluation before a routine recommendation for prophylactic therapy with oral acyclovir can be made. The application of polymerase chain reaction to rapid diagnosis of neonatal HSV disease may provide additional information on which clinical decisions may be based, but its diagnostic utility outside the research setting is still unproven. Further clinical trials for prophylaxis of recurrent SEM disease, prophylactic therapy for the prevention of recurrences of CNS or disseminated disease, the appropriate use of rapid diagnostic testing, and future therapies that may include passive antibody plus antiviral therapy or higher dosage and longer duration of antiviral therapy need to be evaluated.

Anti‐asthma effect of an antiviral drug, acyclovir: a clinical case and experimental study

Although acyclovir (9-(2-hydroxyethoxymethyl) guanine) is an antiviral drug that inhibits DNA polymerase of herpes virus, we have had the experience of an asthmatic patient's peak flow rate being improved by oral administration of acyclovir. The aim of this experiment is whether acyclovir has anti-asthma effects using an asthma model in guinea-pigs. The airway response was induced by a single inhalation of calcium ionophore A23187 (2 mg/mL). The airway obstruction was estimated by the ratio of expiration to inspiration time (E/I). The peribronchial eosinophil infiltration and eosinophil influx into bronchoalveolar lavage (BAL) fluid 7 h after the inhalation were also examined. To assess the effects of acyclovir (1, 10, and 100 mg/kg), aminophylline (20 mg/kg) and pemirolast potassium (TBX, 20 mg/kg) on A23187-induced asthmatic response, the drugs were intraperitoneally administered before the inhalation. The immediate airway obstruction was significantly suppressed by acyclovir (10 mg/kg) and aminophylline, whereas different doses of acyclovir (1 and 100 mg/kg) and TBX showed only a small inhibitory effect on the airway obstruction. On the other hand, the peribronchial eosinophilia was most successfully inhibited by TBX. Acyclovir (10 mg/kg) and aminophylline also suppressed the eosinophilia significantly. Furthermore, acyclovir significantly suppressed eosinophil influx into BAL fluid, whereas aminophylline and TBX weakly suppressed the influx. These results suggest that acyclovir exhibits not only antiviral but also antiasthma activity.