ArticleInternational journal of pharmaceutics2008
Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections.
Article in International journal of pharmaceutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- Amorphization of Low Soluble Drug with Amino Acids to Improve Its Therapeutic Efficacy: a State-of-Art-Review.AAPS PharmSciTech · 2023Review
- Ocular prodrugs: Attributes and challenges.Asian journal of pharmaceutical sciences · 2021Review
- Advancement on Sustained Antiviral Ocular Drug Delivery for Herpes Simplex Virus Keratitis: Recent Update on Potential Investigation.Pharmaceutics · 2020Review
- Ocular surgery after herpes simplex and herpes zoster keratitis.International ophthalmology · 2020Review
- L-Type amino acid transporter 1 as a target for drug delivery.Pharmaceutical research · 2020Review
- Amino Acids in the Development of Prodrugs.Molecules (Basel, Switzerland) · 2018Review
- Development of a Δ9-Tetrahydrocannabinol Amino Acid-Dicarboxylate Prodrug With Improved Ocular Bioavailability.Investigative ophthalmology & visual science · 2017Article
- A comprehensive insight on ocular pharmacokinetics.Drug delivery and translational research · 2016Review
- Ocular cytochrome P450s and transporters: roles in disease and endobiotic and xenobiotic disposition.Drug metabolism reviews · 2014Review
- Novel strategies for anterior segment ocular drug delivery.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2013Review
- Predicting chemical ocular toxicity using a combinatorial QSAR approach.Chemical research in toxicology · 2012Article
- Transporter-targeted lipid prodrugs of cyclic cidofovir: a potential approach for the treatment of cytomegalovirus retinitis.Journal of pharmaceutical sciences · 2012Article
- Transfected MDCK cell line with enhanced expression of CYP3A4 and P-glycoprotein as a model to study their role in drug transport and metabolism.Molecular pharmaceutics · 2012Article
- Ocular sustained release nanoparticles containing stereoisomeric dipeptide prodrugs of acyclovir.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2011Article
- Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability.Acta pharmacologica Sinica · 2010Article
- Enhanced corneal absorption of erythromycin by modulating P-glycoprotein and MRP mediated efflux with corticosteroids.Pharmaceutical research · 2009Article
- Clinical strategies to prevent recurrence of Herpes simplex and Herpes zoster following ocular surgery: A comprehensive review with practical guidelines.Survey of ophthalmologyReview
- Nanotechnology approaches for ocular drug delivery.Middle East African journal of ophthalmologyReview
- Pharmacokinetics of heroin and its metabolites in vitreous humor and blood in a living pig model.Forensic toxicologyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo evaluate in vivo corneal absorption of the amino acid prodrugs of acyclovir (ACV) using a topical well model and microdialysis in rabbits.
methodsStability of L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) prodrugs was evaluated in various ocular tissues. Dose-dependent toxicity of these prodrugs was also examined in rabbit primary corneal epithelial cell culture (rPCEC) using 96-well based cell proliferation assay. In vivo ocular bioavailability of these compounds was also evaluated with a combination of topical well infusion and aqueous humor microdialysis techniques.
resultsAmong the amino acid ester prodrugs, SACV was most stable in aqueous humor. Enzymatic degradation of EACV was the least compared to all other prodrugs. Cellular toxicity of all the prodrugs was significantly less compared to trifluorothymidine (TFT) at 5mM. Absorption rate constants of all the compounds were found to be lower than the elimination rate constants. All the prodrugs showed similar terminal elimination rate constants (lambda(z)). SACV and VACV exhibited approximately two-fold increase in area under the curve (AUC) relative to ACV (p<0.05). Clast (concentration at the last time point) of SACV was observed to be 8+/-2.6microM in aqueous humor which is two and three times higher than VACV and ACV, respectively.
conclusionsAmino acid ester prodrugs of ACV were absorbed through the cornea at varying rates (ka) thereby leading to varying extents (AUC). The amino acid ester prodrug, SACV owing to its enhanced stability, comparable AUC and high concentration at last time point (Clast) seems to be a promising candidate for the treatment of ocular HSV infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.