Abstract
BACKGROUND: Although intravitreal high dose ganciclovir has previously been found to provide excellent control of cytomegalovirus (CMV) retinitis, little was known about the vitreous concentrations of ganciclovir after a 2 mg intravitreal injection. METHODS: Eleven vitreous samples were taken from seven patients with CMV retinitis at 24 and 72 hours after a 2 mg intravitreal injection of ganciclovir and the concentration of ganciclovir was measured by high performance liquid chromatography. RESULTS: The mean concentration of ganciclovir at 24 hours was 143.8 mg/l (95% confidence interval 97.8-190) and at 72 hours was 23.4 mg/l (95% CI 0-49.7). The half life ranged from 11.9 to 26.3 (mean 18.8) hours in the four patients who had two samples taken. The mean half life calculated from the mean concentrations at 24 and 72 hours was 18.3 hours, so the calculated mean concentration at 7 days was 0.6 mg/l. CONCLUSIONS: This suggests that it takes about 7 days to eliminate the intravitreal ganciclovir, and that it is not likely to accumulate with weekly injections. The intravitreal concentrations achieved with high dose therapy remained above the ID50 for CMV (0.25-1.22 mg/l) for up to 7 days.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Daikos G. L., Pulido J., Kathpalia S. B., Jackson G. G. Intravenous and intraocular ganciclovir for CMV retinitis in patients with AIDS or chemotherapeutic immunosuppression. Br J Ophthalmol. 1988 Jul;72(7):521–524. doi: 10.1136/bjo.72.7.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Díaz-Llopis M., Martos M. J., España E., Cervera M., Vila A. O., Navea A., Molina F. J., Romero F. J. Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients. Eperimental toxicity and pharmacokinetics, and clinical trial. Doc Ophthalmol. 1992;82(4):297–305. doi: 10.1007/BF00161017. [DOI] [PubMed] [Google Scholar]
- Freeman W. R., Friedberg D. N., Berry C., Quiceno J. I., Behette M., Fullerton S. C., Munguia D. Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis. Am J Ophthalmol. 1993 Dec 15;116(6):713–720. doi: 10.1016/s0002-9394(14)73471-3. [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]
- Henderly D. E., Freeman W. R., Causey D. M., Rao N. A. Cytomegalovirus retinitis and response to therapy with ganciclovir. Ophthalmology. 1987 Apr;94(4):425–434. doi: 10.1016/s0161-6420(87)33454-2. [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., Sidikaro Y., Kreiger A. E., Hardy D., Sakamoto M. J., Frenkel L. M., Winston D. J., Gottlieb M. S., Bryson Y. J., Champlin R. E. Treatment of cytomegalovirus retinopathy with ganciclovir. Ophthalmology. 1987 Jul;94(7):815–823. doi: 10.1016/s0161-6420(87)33534-1. [DOI] [PubMed] [Google Scholar]
- Jabs D. A., Enger C., Bartlett J. G. Cytomegalovirus retinitis and acquired immunodeficiency syndrome. Arch Ophthalmol. 1989 Jan;107(1):75–80. doi: 10.1001/archopht.1989.01070010077031. [DOI] [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]
- Kuppermann B. D., Quiceno J. I., Flores-Aguilar M., Connor J. D., Capparelli E. V., Sherwood C. H., Freeman W. R. Intravitreal ganciclovir concentration after intravenous administration in AIDS patients with cytomegalovirus retinitis: implications for therapy. J Infect Dis. 1993 Dec;168(6):1506–1509. doi: 10.1093/infdis/168.6.1506. [DOI] [PubMed] [Google Scholar]
- Morlet N., Young S. H. Prevention of intraocular pressure rise following intravitreal injection. Br J Ophthalmol. 1993 Sep;77(9):572–573. doi: 10.1136/bjo.77.9.572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morlet N., Young S., Naidoo D., Fong T., Coroneo M. T. High dose intravitreal ganciclovir for CMV retinitis: a shelf life and cost comparison study. Br J Ophthalmol. 1995 Aug;79(8):753–755. doi: 10.1136/bjo.79.8.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morlet N., Young S., Strachan D., Coroneo M. T. Technique of intravitreal injection. Aust N Z J Ophthalmol. 1993 May;21(2):130–131. doi: 10.1111/j.1442-9071.1993.tb00768.x. [DOI] [PubMed] [Google Scholar]
- Palestine A. G., Polis M. A., De Smet M. D., Baird B. F., Falloon J., Kovacs J. A., Davey R. T., Zurlo J. J., Zunich K. M., Davis M. A randomized, controlled trial of foscarnet in the treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med. 1991 Nov 1;115(9):665–673. doi: 10.7326/0003-4819-115-9-665. [DOI] [PubMed] [Google Scholar]
- Schulman J., Peyman G. A., Horton M. B., Liu J., Barber J. C., Fiscella R., de Miranda P. Intraocular penetration of new antiviral agent, hydroxyacyclovir (BW-B759U). Jpn J Ophthalmol. 1986;30(1):116–124. [PubMed] [Google Scholar]
- Smith T. J., Pearson P. A., Blandford D. L., Brown J. D., Goins K. A., Hollins J. L., Schmeisser E. T., Glavinos P., Baldwin L. B., Ashton P. Intravitreal sustained-release ganciclovir. Arch Ophthalmol. 1992 Feb;110(2):255–258. doi: 10.1001/archopht.1992.01080140111037. [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]
- 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]
- Young S. H., Morlet N., Heery S., Hollows F. C., Coroneo M. T. High dose intravitreal ganciclovir in the treatment of cytomegalovirus retinitis. Med J Aust. 1992 Sep 21;157(6):370–373. doi: 10.5694/j.1326-5377.1992.tb137242.x. [DOI] [PubMed] [Google Scholar]