Pharm Res. 1995 Nov;12(11):1623-7.
Iontophoresis enhances the transport of acyclovir through nude mouse skin by electrorepulsion and electroosmosis.

Volpato NM, Santi P, Colombo P.

Departamento de Tecnologia Farmaceutica, Faculdade de Farmacia, UFRJ, Rio de Janeiro, Brazil.

PURPOSE. Iontophoresis was employed for enhancing the transdermal delivery of acyclovir through nude mouse skin in vitro, with the aim of understanding the mechanisms responsible for drug transport, in order to properly set the conditions of therapeutical application. METHODS. Experiments were done in horizontal diffusion cells, using as donor a saturated solution of acyclovir at two different pH values (3.0 and 7.4). Different electrical conditions (current density and polarity) were employed. RESULTS. At pH 3.0, acyclovir anodal transport was due to electrorepulsion, since acyclovir was 20% in the protonated form. In acyclovir anodal iontophoresis at pH 7.4 the main mechanism involved was electroosmosis, since the drug was substantially unionized and the negative charge of the skin at this pH caused the electroosmotic flow to be from anode to cathode. In the case of cathodal iontophoresis at pH 3.0, acyclovir transport was enhanced approx. seven times, due to the presence of an electroosmotic contribution caused by the reversal of the charge of the skin. At pH 7.4 during cathodal iontophoresis acyclovir transport was not enhanced because the electroosmotic flow was in the opposite direction, compared to drug electric transport, i.e. anode to cathode. The increased skin permeability caused by current application was demonstrated to be less important than electrorepulsion and electroosmosis. CONCLUSIONS. Anodal iontophoresis shows potential applicability for enhancing acyclovir transport to the skin, considering that both electric transport and electroosmosis can be used by appropriately setting the pH of the donor.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8592660&dopt=Abstract acyclovir Zovirax




Med Pregl. 1998 Mar-Apr;51(3-4):151-4.
[Primary infection with varicella-zoster virus in risk groups]

[Article in Croatian]

Jovanovic J, Cvjetkovic D, Pobor M, Brkic S.

Klinika za infektivne i dermato-veneroloske bolesti, Medicinski fakultet, Novi Sad.

INTRODUCTION: Chickenpox represents the primary form of Varicella-zoster virus (VZV) infection and appears most commonly in preschool and school children. The clinical course of chickenpox in immunocompetent children is mainly mild and complications are rare (1-5). Adults and immunocompromised patients are considered to be risk groups for development of serious and even life-threatening complications. The most frequent bacterial complications include secondary bacterial skin infections, angina, sinusitis, otitis and bronchopneumonia. Central nervous system complications, visceral dissemination, pneumonitis and myocarditis are the major viral complications (6,7). Acyclovir is approved for treatment of chickenpox in risk groups to reduce the frequency of viral complications and to treat those ones which have already appeared (7,8). The treatment of bacterial complications is based on the examination results of the bacterial sensitivity to antibiotics. MATERIAL AND METHODS: In our study patients with the diagnosis of chickenpox based on the history of disease, clinical features and clinical course and data on intimate contact with individuals suffering from chickenpox, were clinically followed-up. Sedimentation rate, blood count and urine samples were analyzed. A unique questionnaire was designed to follow-up the following data: sex, age, course of the disease, occurrence of complications in immunocompetent patients and those belonging to risk groups and effects of acyclovir therapy. RESULTS: During a three-year period 48 patients with chickenpox treated at the Clinic of Infectious and Dermatovenereology Diseases have been observed. 64.6% of them were males and 35.4% were females. 29.2% were infants under 1 year of age, 29.2% were 2-13 years of age and 41.6% were 14-50 years of age. According to the clinical course, patients were divided into two groups: the first one included patients who developed complications of chickenpox (54.1%), the second one consisted of those without complications (45.1%). 72.7% of all complications occurred in patients belonging to risk group (14-50 years of age). Among viral complications in risk groups the most common were pneumonia (44.4%) and haemorrhagic rash (44.4%), only one patient (11.1%) developed a mild, viral meningitis. Bacterial complications were also present in risk group as secondary bacterial skin infections (71.4%) and otitis media (28.6%). Viral complications were treated successfully by 750 mg intravenous acyclovir given 3 times a day, or by 800 mg oral acyclovir given 5 times a day during 7-10 days. Adequate antibiotics were used in the treatment of bacterial complications. A case of chickenpox associated with the meningitis caused by Haemophilus influenzae was also reviewed. DISCUSSION: In this study the majority of observed patients had a mild, clinical form of chickenpox that is in accordance with the other available clinical data (1-4). Complications developed more frequently in the adults and usually were of viral etiology. All patients were on time treated with acyclovir and visceral dissemination did not occur in any of them. Complications had a favourable evolution and VZV meningitis was healed without sequelae. Many authors have written about successful use of acyclovir in the treatment of chickenpox. However, acyclovir is not recommended to immunocompetent persons without chickenpox viral complications who do not belong to risk groups (1,3,4,9-11). CONCLUSION: Our findings lead to the conclusion that chickenpox in adults may have an uncertain outcome because of a more severe clinical course and susceptibility to complications. In our study application of acyclovir in that age group provided good results as for prevention and treatment of complications of chickenpox if already manifested.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9611959&dopt=Abstract acyclovir Zovirax




J Pharm Sci. 2001 Mar;90(3):288-97.
Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir.

Fresta M, Fontana G, Bucolo C, Cavallaro G, Giammona G, Puglisi G.

Department of Pharmaceutical Sciences, Viale Andrea Doria 6, I-95125 Catania, Italy.

Acyclovir-loaded polyethyl-2-cyanoacrylate (PECA) nanospheres were prepared by an emulsion polymerization process in the micellar phase and characterized. The influence of the presence of nonionic surfactant as well as other substances [i.e., 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and poly(ethylene glycol) (PEG)], on formulation parameters and loading capacity was investigated. In particular, the presence of PEG resulted in an increase of mean size and size distribution. To obtain PEG-coated PECA nanospheres with a mean size of < 200 nm, Pluronic F68 at concentrations > 1.5% (w/v) should be used during preparation. The presence of PEG also resulted in a change in zeta potential, from -25.9 mV for uncoated nanospheres to -12.2 mV for PEG-coated PECA nanospheres. The presence of HP-beta-CyD elicited an increase of nanosphere size and size distribution, but zeta potential was not influenced. In vitro drug release from nanospheres was determined in both phosphate buffer (pH 7.4) and plasma. The presence of HP-beta-CyD and PEG did not influence the acyclovir release rate in plasma. In the case of release in phosphate buffer, PEG-coated nanospheres showed a slower release. Ocular tolerability of PEG-coated PECA nanospheres was evaluated by the in vivo Draize test. This colloidal carrier was well tolerated, eliciting no particular inflammation at the level of the various ocular structures. In vivo ocular bioavailability was evaluated by instilling 50 microL of the acyclovir-loaded nanospheres only once in the conjunctival sac of rabbit eyes. At various time intervals, aqueous humour acyclovir content was determined by high-performance liquid chromatography. Acyclovir-loaded PEG-coated PECA nanospheres were compared with an aqueous solution of the drug and a physical mixture of acyclovir nanospheres. The acyclovir-loaded PEG-coated PECA nanospheres showed a significant (p < 0.001) increase of drug levels (25-fold) in aqueous humor compared with the free drug or the physical mixture. This finding is probably due to an improved ocular mucoadhesion of PEG-coated PECA nanospheres.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11170022&dopt=Abstract acyclovir Zovirax




Antiviral Res. 1995 May;27(1-2):111-21.
Suppression of infectious virus spread to the liver by foscarnet following lethal infection of acyclovir-resistant herpes simplex virus type 2 in mice.

Li YY, Minagawa H, Tanaka S, Mori R.

Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

Patients with the acquired immune deficiency syndrome (AIDS) occasionally develop hepatitis, pneumonia or esophagitis due to herpes simplex virus type 2 (HSV-2) infection. HSV hepatitis is a rare but serious complication in liver transplantation. Acyclovir-resistant HSV strains may emerge in immunocompromised patients. Following intraperitoneal inoculation, HSV-2 induces necrotizing hepatitis in mice. We studied the virus spread and mortality following intraperitoneal inoculation of HSV-2 RK (an acyclovir-resistant recombinant virus with altered thymidine kinase activity) as compared to its parent virus 8620K. Neither the 50% lethal dose (LD50) nor the average survival time was significantly different between the two strains. Parenteral acyclovir treatment was found to be effective against 8620K but not RK infection. Parenteral foscarnet treatment was effective against both RK and 8620K, and also inhibited the spread of either virus to the liver, spinal cord and brain. Peroral foscarnet administration was found to prevent the virus growth in the liver.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7486949&dopt=Abstract acyclovir Zovirax

UCHSC.edu

OBJECTIVE: To examine clinical associations, evolution of the condition, and response to treatment of erythema multiforme (EM) in prepubertal children. DESIGN: A retrospective case series evaluation of children younger than 13 years with EM. SETTING: Ambulatory care university hospital. PATIENTS: Referral patients from pediatricians serving a population of 3.2 million. INTERVENTIONS: Results of treatment of each EM episode with topical acyclovir or oral acyclovir at a dose of 25 mg/kg per day and 6-month prophylaxis with oral acyclovir at a dose of 20 mg/kg per day were evaluated. OUTCOMES: Age at EM onset, preceding illness, and number and duration of episodes during a 3-year period were recorded. RESULTS: Twelve children (7 boys and 5 girls) in whom herpes simplex virus (HSV)-associated EM developed were evaluated. Preceding lesions were herpes labialis in 8 children and herpes facialis in 2 children. Two children had no obvious HSV lesion. The mean age at onset of disease was 8.1 years, and the mean time from the preceding HSV to the onset of skin lesions was 3.9 days (range, 0-11 days). Episodes of EM lasted a mean of 10.6 days. In 9 children, the EM was recurrent, with a mean of 2.6 episodes per year. All 12 children, including those with negative viral cultures for HSV or no HSV history had HSV detected in their target lesions by polymerase chain reaction amplification of DNA obtained from skin biopsy specimens. Six of 12 children were treated with oral acyclovir at a dose of 25 mg/kg per day for 1 or more individual episodes, without reduction in the episode. Three children underwent 6-month prophylaxis with oral acyclovir at a dose of 20 mg/kg per day and remained disease free during treatment. After discontinuation of the prophylactic treatment with acyclovir, 1 child relapsed at 4 months. The other 2 children had no further episodes during a 3-year period. CONCLUSIONS: The HSV-associated EM is a recurrent disease that can be precipitated by sun exposure and does not progress to Stevens-Johnson syndrome. Childhood HSV-associated EM may be unresponsive to treatment with oral steroids or oral or topical acyclovir. Frequent recurrences of EM may be abrogated by prophylactic treatment with acyclovir.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9343012&dopt=Abstract acyclovir Zovirax