PMID: 11920751Mar 29, 2002Paper

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
Clapton DiasAshim K Mitra

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.

References

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Sep 16, 1999·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·S Walmsley, A Tseng

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Citations

Sep 2, 2008·Pharmaceutical Research·Ripal GaudanaAshim K Mitra
Dec 13, 2006·Nucleosides, Nucleotides & Nucleic Acids·Mariola Koszytkowska-StawińskaErik De Clercq
Jan 23, 2003·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Giridhar S TirucheraiAshim K Mitra
Jan 3, 2006·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Soumyajit MajumdarAshim K Mitra
Aug 17, 2006·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Soumyajit MajumdarAshim K Mitra
Jan 24, 2007·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Sriram GundaAshim K Mitra
Feb 24, 2009·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Kumar G JanoriaAshim K Mitra
Nov 8, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jing ZhangYu-Qing Chen
Aug 9, 2007·Expert Opinion on Drug Delivery·Kumar G JanoriaAshim K Mitra
Oct 9, 2007·Journal of Pharmaceutical Sciences·Yoshihisa Shirasaki
Nov 6, 2009·Journal of Pharmaceutical Sciences·Soumyajit MajumdarRamesh Srirangam
Oct 26, 2005·International Journal of Pharmaceutics·Kunal PatelAshim K Mitra
Apr 26, 2017·Drug Metabolism Reviews·Upendra A ArgikarAndrea J Bushee
Jan 1, 2012·Ophthalmology and Eye Diseases·Afsun Sahin, Pedram Hamrah
Mar 20, 2020·Pharmaceutics·Rubén Varela-FernándezFrancisco J Otero-Espinar
Oct 20, 2005·Journal of Biomolecular Screening·Li DiSusan L Petusky
May 23, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sreeraj Macha, Ashim K Mitra
Jul 5, 2021·Ophthalmology and Therapy·Lixiang WangHui Zhang
Jul 25, 2021·Journal of Pharmacokinetics and Pharmacodynamics·Marc VanhoveAlan W Stitt
Sep 26, 2006·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Feng CaoZheng-Gen Liao

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