Oftalmologia. 1998;42(2):37-41.
[Acyclovir treatment--its effect on visual acuity and the rate of recurrences in herpetic keratitis]

[Article in Romanian]

Corina P.

Clinica Oftalmologica Venizelios-Iraklio, Grecia.

We treated a number of 141 patients suffering of herpetic keratitis--34 were treated with Acyclovir in the first 72 hours the symptoms started, 42 were treated with Acyclovir after this interval and 65 were treated with IDU. We compared visual acuity after six month and we proved that those that were treated with Acyclovir had the same or better visual performances in most cases. Recurrence rate was 0% in the first year and 2.94% in the second year for those witch were treated with Acyclovir in the first 72 hours symptoms started and 2.94% in the first year and 14.71% in the second year for those treated with Acyclovir after this interval. Patients treated with IDU had suffered 23.53% recurrences in the first year and 41.18% recurrences in the second year. Acyclovir treatment and its precociousness protect patients sight and reduce number of recurrences.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9932353&dopt=Abstract acyclovir Zovirax




Nucleosides Nucleotides Nucleic Acids. 2000 Jan-Feb;19(1-2):501-13.
Efficacy of topical acyclovir monophosphate, acyclovir, or penciclovir in orofacial HSV-1 infections of mice and genital HSV-2 infections of guinea pigs.

Kern ER, Palmer J, Szczech G, Painter G, Hostetler KY.

University of Alabama School of Medicine, Birmingham 35294-2170, USA.

The purpose of these studies was to compare the efficacy of acyclovir monophosphate (ACVMP), acyclovir (ACV), or penciclovir (PCV) against HSV-1 in an orofacial infection of mice and against ACV sensitive and resistant genital HSV-2 infections of guinea pigs. Treatment was initiated 24, 48, or 72 hours post inoculation with 5% ACVMP, 5% ACV (Zovirax) or 1% PCV (Denavir). In all experiments, similar efficacy was obtained for ACVMP and ACV, whereas PCV was considerably less effective.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10772730&dopt=Abstract acyclovir Zovirax




J Pharm Sci. 2001 May;90(5):617-24.
Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir.

Yang C, Gao H, Mitra AK.

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri, 5005 Rockhill Road, Kansas City, Missouri 64110, USA.

The objective of this work was to improve nasal absorption of relatively impermeable small drug molecules via an amino acid prodrug approach. Acyclovir was selected as a model drug. L-Aspartate beta-ester, L-lysyl, and L-phenylalanyl esters of acyclovir were synthesized to investigate their effectiveness in enhancing nasal absorption of acyclovir. A stability study was conducted in phosphate buffer under various pH conditions at 25 and 37 degrees C. Enzymatic hydrolysis in rat nasal washings and plasma was conducted at 37 degrees C. A rat in situ nasal perfusion technique was utilized in this investigation to examine the rate and extent of nasal absorption of amino acid prodrugs. The remaining analyte concentrations in the nasal perfusate were quantitated by reversed-phase high-performance liquid chromatography. The results revealed that the L-lysyl and L-phenylalanyl esters were less stable than L-aspartate beta-ester. The stability of all three esters decreased with increasing pH and temperature. L-phenylalanyl ester is highly susceptible to plasma esterases, with an in vitro half-life 1.33 min. The rat in situ nasal perfusion study revealed that the extent of nasal absorption of acyclovir, L-lysyl and L-phenylalanyl esters was not significant (p < 1%). L-Aspartate beta-ester was absorbed to the extent of approximately 8% over 90 min of perfusion at an initial drug concentration of 100 microM. Nasal absorption of L-aspartate beta-ester of acyclovir was inhibited by L-asparagine but not by a dipeptide glycylsarcosine (Gly-Sar). The enhancement of acyclovir nasal absorption from the L-aspartate beta-ester prodrug suggests that nasal uptake of this prodrug probably involves an active transport system. Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11288106&dopt=Abstract acyclovir Zovirax

alpharma.dk

Acyclovir is a widely used agent in the treatment of herpes virus infections of the skin, but owing to its poor physicochemical properties in terms of bioavailability and suboptimal formulations, the treatment is far from optimal. The liquid crystalline cubic phase system has been reported to act as a bioadhesive drug delivery system. In the present study, acyclovir was suspended in a cubic phase of glycerol monooleate (GMO) and water 65%:35% w/w, and the phase behavior and release kinetics were examined. X-ray diffraction and differential scanning calorimetry (DSC) measurements demonstrated that the cubic phase containing 1%-10% (w/w) acyclovir retains its phase condition in the temperature range investigated (20 degrees C-70 degrees C). Acyclovir can be incorporated in high amounts (approximately 40% w/w) without causing phase transition, as is shown in polarized light. This is probably because of its low solubility (approximately 0.11% w/w) in the cubic phase. The release characteristics of acyclovir incorporated as a suspension (1%-5% w/w) into a cubic phase were investigated using Franz diffusion cells. Acyclovir was quantified by high-performance liquid chromatography (HPLC). The drug was readily released from the system, and the release increased with the initial drug load concentration. About 25%-50% was released after 24 h. The release is dependent on the square root of time, and the kinetics can be described by the Higuchi theory. The rate-limiting step in the release process is most likely diffusion. The suggested theory is further supported by identical release data obtained for micronized and nonmicronized acyclovir. The fluxes for 1% and 5% w/w were 380 and 900 microg/h(1/2), respectively. Comparison of the release rates of acyclovir delivered from a cubic phase and from the commercial product, Zovir cream, showed the rate to be six times faster from the cubic phase. The results indicate that the cubic phase is a promising drug delivery system for acyclovir.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11794810&dopt=Abstract acyclovir Zovirax




J Pharmacol Exp Ther. 1999 Nov;291(2):705-9.
Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2.

Sawada K, Terada T, Saito H, Hashimoto Y, Inui KI.

Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.

Peptide transporters (PEPT1 and PEPT2) in epithelia play an important role in the absorption of small peptides and peptide-like drugs. Recently, it was demonstrated that various nonpeptidic compounds can be transported by these transporters. In the present study, we focused on the L-amino acid ester compounds and examined the mechanisms of their interaction with rat PEPTs (rPEPTs) using stable transfectants. Valacyclovir, the L-valyl ester prodrug of the antiherpetic agent acyclovir, competitively inhibited [(14)C]glycylsarcosine uptake in the rPEPT1- or rPEPT2-expressing cells. Dixon plot analyses showed that the inhibition constant (K(i)) values of valacyclovir were 2.7 and 0.22 mM for rPEPT1 and rPEPT2, respectively, suggesting that rPEPT2 had higher affinity for this agent. Various L-valine alkyl esters significantly inhibited [(14)C]glycylsarcosine uptake. L-Valine methyl ester (Val-OMe) competitively inhibited [(14)C]glycylsarcosine uptake with K(i) values of 3.6 and 0.83 mM for rPEPT1 and rPEPT2, respectively, indicating that Val-OMe is also a high-affinity substrate for rPEPT2. Val-OMe had a trans-stimulation effect on [(14)C]glycylsarcosine efflux from both transfectants, suggesting the translocation of L-valine methyl ester via rPEPTs. Val-OMe showed the most potent inhibitory effect among the several L-amino acid methyl esters examined. We conclude that Val-OMe, as well as valacyclovir, could be recognized and transported by rPEPT1 and rPEPT2 and that these L-valyl esters showed higher affinity for rPEPT2 as do most substrates of these transporters. Our results suggest that L-valine is a desirable L-amino acid for the esterification of poorly permeable drugs to enhance their oral bioavailability targeting intestinal PEPT1.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10525090&dopt=Abstract acyclovir Zovirax