Abstract
Acyclovir diphosphate dimyristoylglycerol (ACVDP-DG) is a lipid prodrug which is active against ACV-resistant strains of herpes simplex virus because of its intracellular metabolism to ACV monophosphate. In human cytomegalovirus (HCMV)-infected MRC-5 cells, ACVDP-DG was ninefold more active than ACV. When liposomal [8-3H]ACVDP-DG was injected intravitreally at the maximum nontoxic dose of 1 mumol in rabbits, the drug remained above its estimated 90% HCMV-inhibitory concentration for 18 days. Intravitreal ganciclovir persists above its 90% inhibitory concentration for only 1 to 2 days. ACVDP-DG may be useful as a local treatment for HCMV retinitis.
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- Cantrill H. L., Henry K., Melroe N. H., Knobloch W. H., Ramsay R. C., Balfour H. H., Jr Treatment of cytomegalovirus retinitis with intravitreal ganciclovir. Long-term results. Ophthalmology. 1989 Mar;96(3):367–374. doi: 10.1016/s0161-6420(89)32900-9. [DOI] [PubMed] [Google Scholar]
- Dolnak D. R., Munguia D., Wiley C. A., De Clercq E., Bergeron-Lynn G. L., Boscher C., Connor J. D., Sherwood C., Capparelli E., Armani R. Lack of retinal toxicity of the anticytomegalovirus drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine. Invest Ophthalmol Vis Sci. 1992 Apr;33(5):1557–1563. [PubMed] [Google Scholar]
- Díaz-Llopis M., Chipont E., Sanchez S., España E., Navea A., Menezo J. L. Intravitreal foscarnet for cytomegalovirus retinitis in a patient with acquired immunodeficiency syndrome. Am J Ophthalmol. 1992 Dec 15;114(6):742–747. doi: 10.1016/s0002-9394(14)74054-1. [DOI] [PubMed] [Google Scholar]
- Erice A., Chou S., Biron K. K., Stanat S. C., Balfour H. H., Jr, Jordan M. C. Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. N Engl J Med. 1989 Feb 2;320(5):289–293. doi: 10.1056/NEJM198902023200505. [DOI] [PubMed] [Google Scholar]
- FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
- Fanning M. M., Read S. E., Benson M., Vas S., Rachlis A., Kozousek V., Mortimer C., Harvey P., Schwartz C., Chew E. Foscarnet therapy of cytomegalovirus retinitis in AIDS. J Acquir Immune Defic Syndr. 1990;3(5):472–479. [PubMed] [Google Scholar]
- Faulds D., Heel R. C. Ganciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infections. Drugs. 1990 Apr;39(4):597–638. doi: 10.2165/00003495-199039040-00008. [DOI] [PubMed] [Google Scholar]
- Freeman W. R. Intraocular antiviral therapy. Arch Ophthalmol. 1989 Dec;107(12):1737–1739. doi: 10.1001/archopht.1989.01070020819020. [DOI] [PubMed] [Google Scholar]
- Freeman W. R., Lerner C. W., Mines J. A., Lash R. S., Nadel A. J., Starr M. B., Tapper M. L. A prospective study of the ophthalmologic findings in the acquired immune deficiency syndrome. Am J Ophthalmol. 1984 Feb;97(2):133–142. doi: 10.1016/s0002-9394(14)76082-9. [DOI] [PubMed] [Google Scholar]
- Gross J. G., Bozzette S. A., Mathews W. C., Spector S. A., Abramson I. S., McCutchan J. A., Mendez T., Munguia D., Freeman W. R. Longitudinal study of cytomegalovirus retinitis in acquired immune deficiency syndrome. Ophthalmology. 1990 May;97(5):681–686. doi: 10.1016/s0161-6420(90)32552-6. [DOI] [PubMed] [Google Scholar]
- Heinemann M. H. Long-term intravitreal ganciclovir therapy for cytomegalovirus retinopathy. Arch Ophthalmol. 1989 Dec;107(12):1767–1772. doi: 10.1001/archopht.1989.01070020849025. [DOI] [PubMed] [Google Scholar]
- Henry K., Cantrill H., Fletcher C., Chinnock B. J., Balfour H. H., Jr Use of intravitreal ganciclovir (dihydroxy propoxymethyl guanine) for cytomegalovirus retinitis in a patient with AIDS. Am J Ophthalmol. 1987 Jan 15;103(1):17–23. doi: 10.1016/s0002-9394(14)74163-7. [DOI] [PubMed] [Google Scholar]
- Holland G. N., Pepose J. S., Pettit T. H., Gottlieb M. S., Yee R. D., Foos R. Y. Acquired immune deficiency syndrome. Ocular manifestations. Ophthalmology. 1983 Aug;90(8):859–873. doi: 10.1016/s0161-6420(83)80009-8. [DOI] [PubMed] [Google Scholar]
- Hostetler K. Y., Parker S., Sridhar C. N., Martin M. J., Li J. L., Stuhmiller L. M., van Wijk G. M., van den Bosch H., Gardner M. F., Aldern K. A. Acyclovir diphosphate dimyristoylglycerol: a phospholipid prodrug with activity against acyclovir-resistant herpes simplex virus. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11835–11839. doi: 10.1073/pnas.90.24.11835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuppermann B. D., Flores-Aguilar M., Quiceno J. I., Rickman L. S., Freeman W. R. Combination ganciclovir and foscarnet in the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Arch Ophthalmol. 1993 Oct;111(10):1359–1366. doi: 10.1001/archopht.1993.01090100067029. [DOI] [PubMed] [Google Scholar]
- Palestine A. G., Rodrigues M. M., Macher A. M., Chan C. C., Lane H. C., Fauci A. S., Masur H., Longo D., Reichert C. M., Steis R. Ophthalmic involvement in acquired immunodeficiency syndrome. Ophthalmology. 1984 Sep;91(9):1092–1099. doi: 10.1016/s0161-6420(84)34201-4. [DOI] [PubMed] [Google Scholar]
- Sarraf D., Equi R. A., Holland G. N., Yoshizumi M. O., Lee D. A. Transscleral iontophoresis of foscarnet. Am J Ophthalmol. 1993 Jun 15;115(6):748–754. doi: 10.1016/s0002-9394(14)73642-6. [DOI] [PubMed] [Google Scholar]
- Schulman J., Peyman G. A., Horton M. B., Liu J., Fiscella R., Pulido J., Barber J. C., de Miranda P. Intraocular 9-([2-hydroxy-1-(hydroxymethyl) ethoxy] methyl) guanine levels after intravitreal and subconjunctival administration. Ophthalmic Surg. 1986 Jul;17(7):429–432. [PubMed] [Google Scholar]
- She S. C., Peyman G. A., Schulman J. A. Toxicity of intravitreal injection of foscarnet in the rabbit eye. Int Ophthalmol. 1988;12(2):151–154. doi: 10.1007/BF00137142. [DOI] [PubMed] [Google Scholar]
- Ussery F. M., 3rd, Gibson S. R., Conklin R. H., Piot D. F., Stool E. W., Conklin A. J. Intravitreal ganciclovir in the treatment of AIDS-associated cytomegalovirus retinitis. Ophthalmology. 1988 May;95(5):640–648. doi: 10.1016/s0161-6420(88)33147-7. [DOI] [PubMed] [Google Scholar]
- Wahren B., Oberg B. Reversible inhibition of cytomegalovirus replication by phosphonoformate. Intervirology. 1980;14(1):7–15. doi: 10.1159/000149156. [DOI] [PubMed] [Google Scholar]
- Yoshizumi M. O., Lee D., Vinci V., Fajardo S. Ocular toxicity of multiple intravitreal DHPG injections. Graefes Arch Clin Exp Ophthalmol. 1990;228(4):350–355. doi: 10.1007/BF00920061. [DOI] [PubMed] [Google Scholar]