Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2529-34.
In vivo antiviral efficacy of a dipeptide acyclovir prodrug, val-val-acyclovir, against HSV-1 epithelial and stromal keratitis in the rabbit eye model.

Anand BS, Hill JM, Dey S, Maruyama K, Bhattacharjee PS, Myles ME, Nashed YE, Mitra AK.

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri 64110-2499, USA.

PURPOSE: A dipeptide prodrug of the antiviral nucleoside acyclovir (ACV), val-val-ACV (VVACV), was evaluated in vivo as a potential drug candidate for improving antiviral efficacy against herpetic epithelial and stromal keratitis. METHODS: The effect of 1% VVACV on epithelial keratitis induced by inoculation of HSV-1 strain McKrae (25 microL of 10(5) plaque-forming units [PFU]) in the scarified rabbit cornea and stromal keratitis induced by intrastromal injection of HSV-1 strain RE (10 microL of 10(5) PFU) was compared with that of 1% trifluorothymidine (TFT) and balanced salt solution as the vehicle control. Both eyes of 10 rabbits were used in each treatment group. Lesions were evaluated by slit lamp examinations over a 2-week period after infection. Aqueous humor samples and corneas were analyzed for drug concentrations at the end of each experiment. Cytotoxicity of VVACV in comparison with val-acyclovir (VACV), ACV, and TFT was evaluated in cellular proliferation assays. RESULTS: The dipeptide prodrug VVACV demonstrated excellent activity against HSV-1 in the rabbit epithelial and stromal keratitis models: 1% VVACV was as effective as 1% TFT. The prodrug was also less cytotoxic than TFT, which is the only effective drug currently licensed and routinely used for topical treatment of ocular herpes infections in the United States. CONCLUSIONS: The less cytotoxic and highly water-soluble prodrug VVACV, which showed excellent in vivo activity against HSV-1 in rabbit epithelial and stromal keratitis, is a promising drug candidate for treatment of ocular HSV infections.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12766053&dopt=Abstract acyclovir Zovirax




J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 5;791(1-2):357-63.
Technique validation by liquid chromatography for the determination of acyclovir in plasma.

Fernandez M, Sepulveda J, Aranguiz T, von Plessing C.

Pharmacy Department, Pharmacy Faculty, Universidad de Concepcion, Casilla 237, Concepcion, Chile.

In this research project, a high-performance liquid chromatography (HPLC) method was developed for the determination of acyclovir (ACV) in plasma. The plasma samples, recharged with acyclovir and in presence of 5'-N-methylcarboxyamidoadenosine (MECA) as an internal standard, were purified using a solid-phase extraction technique with Waters Oasis HLB columns. The separation of the components from the extract was carried out in a LiChrospher 100 RP-18 column for further ultraviolet detection at a wavelength range of 250-260 nm. The mobile phase composition was 18% acetonitrile, sodium dodecylsulphate 5 mM and phosphate buffer at pH 2.6 with an analysis time of 13 min per sample. The average retention time for acyclovir was of 5.0 min and for the internal standard 11.2 min. The calibration curve was linear ranging between 0.05 and 1.80 microg/ml. The detection limit was 0.006 microg/ml with a quantification limit of 0.020 microg/ml. The ACV recuperation percentage for 250 microl of plasma was between 94.7 and 109.7% with a coefficient of variation not higher than 5.2%. This method was developed and validated for use in bioavailability and bioequivalence studies.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12798195&dopt=Abstract acyclovir Zovirax[PubMed - in process]

ratree.psu.ac.th

This study aimed to examine the risk of adverse pregnancy outcomes in children born to mothers who redeemed a prescription for systemic or topical acyclovir during pregnancy. Data on prescriptions of acyclovir were obtained from the Danish North Jutland Prescription Database and data on pregnancy outcomes from the Danish Medical Birth Registry and the County Hospital Discharge Registry. The risk of malformations, low birth weight, preterm birth and stillbirth in users of acyclovir were compared with non-exposed women using a follow-up design, while the risk of spontaneous abortion was examined using a case-control design. 90 pregnant women had redeemed a prescription for systemic acyclovir, and 995 women for topical acyclovir, during 30 d before conception, or during their pregnancies from 1 January 1990 to 31 December 2001. The odds ratios (95% confidence intervals) of the exposed relative to the non-exposed for the systemic and topical acyclovir were: malformations, 0.69 (0.17-2.82) and 0.84 (0.51, 1.39); low birth weight, 2.03 (0.50-8.35) and 0.48 (0.21-1.07); preterm birth, 1.04 (0.38-2.85) and 0.95 (0.70-1.28); stillbirth (for topical acyclovir), 1.70 (0.80-3.60); and spontaneous abortion, 2.16 (0.60-7.80) and 1.29 (0.80-3.60). There is increasing evidence that the use of systemic acyclovir is not associated with an increased prevalence of malformations at birth and preterm delivery. The data for low birth weight and spontaneous abortion are still inconclusive, although the risk of spontaneous abortion is increased in women exposed to acyclovir during the first month of pregnancy. The use of topical acyclovir does not seem to be associated with any adverse pregnancy outcome, although data on stillbirth are inconclusive.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12839155&dopt=Abstract acyclovir Zovirax

med.nagoya-u.ac.jp

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.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12855237&dopt=Abstract acyclovir Zovirax

uni-duesseldorf.de

PURPOSE: The main reasons for graft failure following penetrating keratoplasty in patients with herpetic eye disease are recurrence of herpetic disease and allograft rejection. In a randomised trial the effect of systemic acyclovir and mycophenolate mofetil (MMF) on these post-keratoplasty complications was evaluated. PATIENTS AND METHODS: Patients with typical clinical findings of recurrent herpetic keratitis were enrolled in this single-centre study after contraindications to systemic immunosuppression were ruled out. In a prospective randomised trial 30 patients were treated in three groups. In group A patients received acyclovir 200 mg five times/day for 3 weeks. In group B patients were treated with acyclovir 200 mg five times/day for 1 year, and patients in group C received acyclovir 200 mg five times/day in combination with MMF 1 g twice daily for 1 year. RESULTS: In group A 3 patients experienced seven herpes recurrences. One patient had a moderate and one further patient a severe allograft rejection. In group B three severe allograft rejections were observed. Herpes recurrences did not occur while receiving acyclovir prophylaxis, but only once after the prophylaxis had been stopped. In group C no herpes recurrence was observed, and only two mild allograft rejections occurred while being under combined acyclovir-MMF therapy. Another mild and one moderate allograft rejection were observed after cessation of MMF. CONCLUSIONS: These results demonstrate that systemic acyclovir protects the grafts from recurrences of herpetic disease as long as it is administered at efficient doses. Simultaneously administered mycophenolate mofetil does not trigger herpes recurrences and protects the graft from severe allograft rejections, but mild, less dangerous immune reactions may still occur while receiving MMF. The combination of systemic acyclovir and mycophenolate mofetil therefore is recommended for patients at high risk for herpes recurrence and allograft rejections.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12928902&dopt=Abstract acyclovir Zovirax[PubMed - in process]