vision.eei.upmc.edu

PURPOSE: The goal of this was to determine whether the systemic administration of valacyclovir (Valtrex) would reduce ocular shedding of herpes simplex virus 1 (HSV-1) after excimer laser ablation in the New Zealand rabbit latency model. METHODS: The in vitro 50% inhibitory concentration (IC50) of HSV-1 W strain was determined by using a plaque-reduction assay to verify its sensitivity to acyclovir. Forty-seven NZW rabbits latently infected with HSV-1 W strain were divided into four groups: I, 50 mg/kg/day valacyclovir; II, 100 mg/kg/day valacyclovir; III, 150 mg/kg/day valacyclovir; and IV, saline control. One half of the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with one dose before excimer laser keratectomy. HSV-1 ocular shedding was determined from eye cultures for 7 days after treatment. RESULTS: The IC50 for HSV-1 W was determined to be 2.9 microg/ml. The administration of both 100 mg/kg/day (group II) and 150 mg/kg/day (group III) of valacyclovir significantly reduced the number of eyes from which latent HSV-1 was recovered compared with the control group. There was no difference between the control group and group I (50 mg/kg/day valacyclovir). However, all three valacyclovir dosages significantly reduced the total number of HSV-1 shedding days compared with the control group, and 100% HSV-1 TG latency was demonstrated for all four groups. CONCLUSION: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding in a dose-dependent manner after excimer laser keratectomy in the NZW rabbit latency model.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10571301&dopt=Abstract acyclovir Zovirax




Arch Toxicol. 1997;71(9):556-62.
Toxic effect of concomitant administration of cyclosporin A and acyclovir on renal function and morphology in rats.

Hannemann J, Wunderle W, Yousif T, Kruger S, Baumann K.

Department of Internal Medicine II, Medical University of Lubeck, Germany.

The immunosuppressive agent cyclosporin A (CyA) and the antiviral drug acyclovir may cause renal functional impairment. CyA-induced immunosuppression increases the rate of viral infections. Therefore we were interested to determine whether short-term co-administration of CyA and acyclovir involves an increased nephrotoxic risk. Male Wistar rats were treated with CyA (20 mg/kg body wt., s.c., once daily for 8 days), acyclovir (15 mg/kg body wt., s.c., 3-times daily for the last 5 days) or a combination of CyA and acyclovir. Blood levels of CyA were determined after a single dose. Urine was monitored for volume, osmolality, total protein and N-acetyl-beta-D-glucosaminidase (beta-NAG). Concentrations of blood urea nitrogen (BUN) and plasma-creatinine were determined (day 9). Renal cortical slices were monitored for accumulation of weak organic acids (para-aminohippurate, PAH) and bases (tetra-ethylammonium, TEA) and for malondialdehyde (MDA) content. Renal histology was also examined. CyA induced a decrease in body and kidney weight, in urine osmolality and in the excretion of total protein. Plasma-creatinine and BUN as well as MDA content of renal tissues were increased by CyA. Acyclovir alone did not induce significant changes. In comparison to CyA values, urine volume and beta-NAG excretion were enhanced and TEA accumulation depressed by the concomitant administration of CyA and acyclovir. CyA- or acyclovir-treatment alone did not result in significant morphological changes. In the group co-administered CyA/acyclovir, the kidneys showed mild to moderate signs of tubulopathy. Short-term co-administration of CyA and acyclovir was concluded to have possibly increased nephrotoxic potential.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9285038&dopt=Abstract acyclovir Zovirax

msx.upmc.edu

PURPOSE: To determine whether the systemic administration of valacyclovir (Valtrex) reduces ocular shedding of herpes simplex virus type 1 (HSV-1) after laser in situ keratomileusis (LASIK) in the New Zealand White (NZW) rabbit latency model. SETTING: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. METHODS: New Zealand White rabbits latently infected with HSV-1 W strain were divided into 3 groups. The first received 100 mg/kg/day of valacyclovir; the second, 200 mg/kg/day of valacyclovir; and the third (control), saline. One half the total dose of valacyclovir was delivered via intraperitoneal injections twice daily for 7 days beginning with 1 dose before LASIK. The HSV-1 ocular shedding was determined from eye cultures for 7 days after LASIK. RESULTS: The administration of both 100 mg/kg/day and 200 mg/kg/day of valacyclovir significantly reduced the number of eyes (1/16 in both groups) and the total number of HSV-1 shedding days (1/122 and 2/122, respectively) from which HSV-1 was recovered compared to the control group (7/16 [P =.0396] and 14/129 [P <.007], respectively). CONCLUSIONS: Systemic administration of valacyclovir significantly reduced HSV-1 ocular shedding after LASIK in the NZW rabbit latency model. The clinical implications of this study suggest that patients with a history of recurrent ocular herpes may be able to safely have LASIK with less risk of a recurrent herpetic episode while on valacyclovir antiviral prophylaxis.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11524202&dopt=Abstract acyclovir Zovirax




Antibiot Khimioter. 2000;45(1):5-9.
[Inhibition of the reproduction of strains of the herpes simplex virus type 1 with drug resistance]

[Article in Russian]

Andronova VL, Galegov GA.

D. I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Moscow.

Inhibition of type-1 herpes simplex strains resistant to acyclovir, phosphonoacetic acid and their combination by combined use of three drugs with different mechanisms of action capable of suppressing reproduction of the acyclovir resistant strain was studied. The combinations used were the following: Ara-A + ribavirin + phosphonoformic acid, Xylo-A + ribavirin + phosphonoformic acid and Ph-ACH + Ara-A + ribavirin. The former two combinations had a synergistic action on the standard strain L2 whose drug susceptibility had not undergone changes as well as on the acyclovir resistant strain. As for the strain resistant to phosphonoacetic acid and to acyclovir + phosphonoacetic acid the effect was additive. Ph-ACH + Ara-A + ribavirin had a marked synergistic action on all the strains tested.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10690421&dopt=Abstract acyclovir Zovirax




Acta Ophthalmol Scand. 1996 Jun;74(3):265-70.
Herpetic stromal disease: response to acyclovir/steroid therapy.

O'Brien WJ, Segundo AP, Guy J, Dorn EM, Taylor JL.

Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, USA.

The efficacy of combined acyclovir and steroid therapy in the treatment of herpetic stromal disease was evaluated by clinical evaluation of disease, the rebound of disease following termination of therapy, and the recovery of virus and viral DNA from corneas in a rabbit model. Therapy with acyclovir alone produced a significant reduction in corneal thickness in 10% of eyes. Addition of steroid to acyclovir therapy decreased the severity of stromal disease as measured by corneal thickness and increased the frequency of response to treatment to 63% of eyes. All eyes receiving acyclovir alone experienced rebound of disease following termination of therapy. Combined therapy increased the severity of rebound of corneal disease. Virus was recovered from cell cultures established after recovery from rebound in 50% of untreated and treated eyes. Viral DNA was detected by PCR in five of the nine corneal cultures which did not produce infectious virus.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8828724&dopt=Abstract acyclovir Zovirax