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Effect of mono- and di-acylation on the ocular disposition of ganciclovir: physicochemical properties, ocular bioreversion, and antiviral activity of short chain ester prodrugs.
J Pharm Sci 2002; 91(3):660-8JP

Abstract

A series of short-chain carboxylic mono- and diesters of ganciclovir were synthesized in our laboratory. Physico-chemical properties, i.e., solubility (pH 4.2), partition coefficient in 1-octanol/phosphate buffer (pH 7.4), aqueous stability at various pH values, bioreversion kinetics in various ocular homogenates and effectiveness against various Herpes viruses in vitro were determined. The compounds exhibited a decrease in solubility as the ester length ascended with a corresponding increase in the octanol/buffer partition coefficient values. All of the prodrugs exhibit stability profiles typical of a carboxylic ester with maximum stability at neutral or slight acidic pH (4.0-7.0). Apparent first-order rate constants associated with prodrug to drug hydrolysis in the ocular homogenates varied depending on the size of the promoiety, lipophilicity of the compound, and the ocular tissue studied. The acetyl and butyryl mono and diesters were screened against various Herpes viruses. The monobutyrate ester of ganciclovir exhibits excellent activity against HSV-2 and VZV and provides a very high selectivity index against most of the viruses studied.

Authors+Show Affiliations

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11920751

Citation

Dias, Clapton S., et al. "Effect of Mono- and Di-acylation On the Ocular Disposition of Ganciclovir: Physicochemical Properties, Ocular Bioreversion, and Antiviral Activity of Short Chain Ester Prodrugs." Journal of Pharmaceutical Sciences, vol. 91, no. 3, 2002, pp. 660-8.
Dias CS, Anand BS, Mitra AK. Effect of mono- and di-acylation on the ocular disposition of ganciclovir: physicochemical properties, ocular bioreversion, and antiviral activity of short chain ester prodrugs. J Pharm Sci. 2002;91(3):660-8.
Dias, C. S., Anand, B. S., & Mitra, A. K. (2002). Effect of mono- and di-acylation on the ocular disposition of ganciclovir: physicochemical properties, ocular bioreversion, and antiviral activity of short chain ester prodrugs. Journal of Pharmaceutical Sciences, 91(3), pp. 660-8.
Dias CS, Anand BS, Mitra AK. Effect of Mono- and Di-acylation On the Ocular Disposition of Ganciclovir: Physicochemical Properties, Ocular Bioreversion, and Antiviral Activity of Short Chain Ester Prodrugs. J Pharm Sci. 2002;91(3):660-8. PubMed PMID: 11920751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of mono- and di-acylation on the ocular disposition of ganciclovir: physicochemical properties, ocular bioreversion, and antiviral activity of short chain ester prodrugs. AU - Dias,Clapton S, AU - Anand,Banmeet S, AU - Mitra,Ashim K, PY - 2002/3/29/pubmed PY - 2002/6/28/medline PY - 2002/3/29/entrez SP - 660 EP - 8 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 91 IS - 3 N2 - A series of short-chain carboxylic mono- and diesters of ganciclovir were synthesized in our laboratory. Physico-chemical properties, i.e., solubility (pH 4.2), partition coefficient in 1-octanol/phosphate buffer (pH 7.4), aqueous stability at various pH values, bioreversion kinetics in various ocular homogenates and effectiveness against various Herpes viruses in vitro were determined. The compounds exhibited a decrease in solubility as the ester length ascended with a corresponding increase in the octanol/buffer partition coefficient values. All of the prodrugs exhibit stability profiles typical of a carboxylic ester with maximum stability at neutral or slight acidic pH (4.0-7.0). Apparent first-order rate constants associated with prodrug to drug hydrolysis in the ocular homogenates varied depending on the size of the promoiety, lipophilicity of the compound, and the ocular tissue studied. The acetyl and butyryl mono and diesters were screened against various Herpes viruses. The monobutyrate ester of ganciclovir exhibits excellent activity against HSV-2 and VZV and provides a very high selectivity index against most of the viruses studied. SN - 0022-3549 UR - https://www.unboundmedicine.com/medline/citation/11920751/Effect_of_mono__and_di_acylation_on_the_ocular_disposition_of_ganciclovir:_physicochemical_properties_ocular_bioreversion_and_antiviral_activity_of_short_chain_ester_prodrugs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(16)30941-8 DB - PRIME DP - Unbound Medicine ER -