Acyclovir in the Treatment of Herpetic Stromal Disease

Sanitato, James J.; Asbell, Penny A.; Varnell, Emily D.; Kissling, Grace E.; Kaufman, Herbert E.

doi:10.1016/0002-9394(84)90237-x

Cited by 49 publications

(10 citation statements)

References 23 publications

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“…Acyclovir, valacyclovir, and other nucleoside analogues are effective in the treatment of HSV-1 keratitis in animal models 33–35. We have also shown that cyclooxygenase (COX) inhibitors, such as aspirin, have the ability to reduce HSV-1 shedding in animals after thermal stress 36,37.…”

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confidence: 99%

A Double-Blind Placebo-Controlled Study to Evaluate Valacyclovir Alone and with Aspirin for Asymptomatic HSV-1 DNA Shedding in Human Tears and Saliva

Kumar

Hill

Clément

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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Purpose To test the effect of valacyclovir alone and with aspirin on the asymptomatic shedding of HSV-1 DNA in tears and saliva of healthy individuals. Method The subjects (n = 45) were randomized into three groups without regard to age, sex, or race. Group 1 (n = 14) received the placebo, group 2 (n = 15) received a dose of 500 mg valacyclovir once daily, and group 3 (n = 16) received a dose of 500 mg valacyclovir once daily and 350 mg aspirin twice daily for 30 days. Ocular and oral swabs were collected twice daily for 30 days. DNA was extracted from all swabs and HSV-1 DNA copy numbers were determined. Statistical analysis was performed to compare the DNA copy numbers of the three groups. Results There was no significant difference in the HSV-1 DNA copy numbers in the tears or saliva among any of the three treatment groups. The mean copy numbers ± SE of mean (SEM) of HSV-1 DNA in tears were 340 ± 35, 1074 ± 320, and 630 ± 51 for groups 1, 2, and 3, and in saliva were 238 ± 35, 963 ± 462, and 493 ± 25, respectively, for groups 1, 2, and 3. Conclusions No correlation was found between HSV-1 shedding and valacyclovir and valacyclovir with aspirin treatment. The HSV-1 DNA copy number was not reduced by treatment with 500 mg of valacyclovir daily or with a combination of daily valacyclovir (500 mg) plus twice-daily doses of aspirin (350 mg) over 30 days.

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A Double-Blind Placebo-Controlled Study to Evaluate Valacyclovir Alone and with Aspirin for Asymptomatic HSV-1 DNA Shedding in Human Tears and Saliva

Kumar

Hill

Clément

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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“…The selections were based on existing reported use of acyclovir for the treatment of ocular Herpes Simplex Virus (HSV) keratitis, one common cause of corneal (infectious) blindness. (Tabbara and Al Balushi, 2010) The HSV infection of the cornea is characterized by progression of viral replication in three distinct regions of the cornea: the epithelium, the stroma, and posterior region (following cornea perforation) (Grant, 1987;Liesegang et al, 1989;Sanitato et al, 1984). Acyclovir is a wellestablished synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV) (Acosta and Flexner, 2011).…”

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Formulation and process factors influencing product quality and in vitro performance of ophthalmic ointments

Al-Ghabeish

Rahman

et al. 2015

International Journal of Pharmaceutics

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“…Acyclovir, an antiviral nucleoside, possesses activity against human herpesviruses. Owing to its limited bioavailability, the drug has shown moderate antiviral efficacy after oral (Steingrimsdottir et al, 2000) and topical administration (Sanitato et al, 1984). After oral and topical administration, VACV is rapidly and completely converted in vivo by enzymatic hydrolysis to acyclovir, the active parent drug.…”

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Interactions of the Dipeptide Ester Prodrugs of Acyclovir with the Intestinal Oligopeptide Transporter: Competitive Inhibition of Glycylsarcosine Transport in Human Intestinal Cell Line-Caco-2

Anand¹,

Patel²,

Mitra³

2003

J Pharmacol Exp Ther

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The oligopeptide transporter may be exploited to enhance the absorption of drugs by synthesizing their dipeptide ester prodrugs, which may be recognized as its substrates. Various dipeptide esters of acyclovir (ACV), an antiviral nucleoside analog, were synthesized. Enzymatic hydrolysis and affinity of the prodrugs toward the human intestinal peptide transporter hPEPT1 were studied using the human intestinal Caco-2 cell line. Affinity studies were performed by inhibiting the uptake of [ 3 H]glycylsarcosine by the prodrugs. The uptake of glycylsarcosine was found to be saturable at higher concentrations and was competitively inhibited by the prodrugs of ACV. All prodrugs except Tyr-Gly-ACV demonstrated a higher affinity (1.41-4.96 mM) toward hPEPT1 than cephalexin (8.19 Ϯ 2.12 mM), which was used as a positive control. Two prodrugs, Gly-Val-ACV and Val-Val-ACV, showed comparable affinity to Val-ACV, an amino acid prodrug of ACV recognized by PEPT1/PEPT2. The permeability of Gly-Val-ACV (2.99 Ϯ 0.59 ϫ 10 Ϫ6 cm/s) across Caco-2 was comparable with that of Val-ACV (3.01 Ϯ 0.21 ϫ 10 Ϫ6 cm/s) and was significantly inhibited (63%) in presence of glycylsarcosine. The transport of GVACV across Caco-2 was saturable at higher concentrations, and the parameters were calculated as K m 3.16 Ϯ 0.31 mM and V max 0.014 Ϯ 0.00058 nmol cm Ϫ2 min Ϫ1 . Overall, the results suggest that the dipeptide prodrugs of ACV have a high affinity toward the intestinal oligopeptide transporter hPEPT1 and therefore seem to be promising candidates in the treatment of ocular and oral herpesvirus infections, because cornea and intestinal epithelia seem to express the oligopeptide transporters.

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Acyclovir in the Treatment of Herpetic Stromal Disease

Cited by 49 publications

References 23 publications

A Double-Blind Placebo-Controlled Study to Evaluate Valacyclovir Alone and with Aspirin for Asymptomatic HSV-1 DNA Shedding in Human Tears and Saliva

A Double-Blind Placebo-Controlled Study to Evaluate Valacyclovir Alone and with Aspirin for Asymptomatic HSV-1 DNA Shedding in Human Tears and Saliva

Formulation and process factors influencing product quality and in vitro performance of ophthalmic ointments

Interactions of the Dipeptide Ester Prodrugs of Acyclovir with the Intestinal Oligopeptide Transporter: Competitive Inhibition of Glycylsarcosine Transport in Human Intestinal Cell Line-Caco-2

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