Vitreous Pharmacokinetics and Electroretinographic Findings After Intravitreal Injection of Acyclovir in Rabbits

Overview

Journal Clinics (Sao Paulo)

Publisher Elsevier

Specialty General Medicine

Date 2012 Sep 6

PMID 22948462

Citations 5

Authors

Francisco Max Damico

Mariana Ramos Scolari

Gabriela Lourencon Ioshimoto

Beatriz Sayuri Takahashi

Armando da Silva Cunha Jr

Silvia Ligorio Fialho

Daniela Maria Bonci

Fabio Gasparin

Dora Fix Ventura

Affiliations

Soon will be listed here.

Abstract

Objectives: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina.

Methods: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision.

Results: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes.

Conclusions: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina.

Citing Articles

Corosolic acid: antiangiogenic activity and safety of intravitreal injection in rats eyes.

Rodrigues Toledo C, Viana Pereira V, Dourado L, Paiva M, Silva-Cunha A Doc Ophthalmol. 2019; 138(3):181-194.

PMID: 30809742 DOI: 10.1007/s10633-019-09682-x.

Intravitreal injection of the synthetic peptide LyeTx I b, derived from a spider toxin, into the rabbit eye is safe and prevents neovascularization in a chorio-allantoic membrane model.

Silva F, Paiva M, Dourado L, Silva R, Nunes da Silva C, Lopes da Costa B J Venom Anim Toxins Incl Trop Dis. 2018; 24:31.

PMID: 30479614 PMC: 6249906. DOI: 10.1186/s40409-018-0168-5.

Toxicity and in vivo release profile of sirolimus from implants into the vitreous of rabbits' eyes.

Paiva M, Lage N, Guerra M, Mol M, Ribeiro M, Fulgencio G Doc Ophthalmol. 2018; 138(1):3-19.

PMID: 30456454 DOI: 10.1007/s10633-018-9664-8.

Comparison between albino and pigmented rabbit ERGs.

Ioshimoto G, Camargo A, Liber A, Nagy B, Damico F, Ventura D Doc Ophthalmol. 2018; 136(2):113-123.

PMID: 29572760 DOI: 10.1007/s10633-018-9628-z.

Test-retest reliability of scotopic full-field electroretinograms in rabbits.

Luebke J, Anton A, Bach M Doc Ophthalmol. 2017; 134(3):157-165.

PMID: 28303363 DOI: 10.1007/s10633-017-9582-1.

References

Pastore A, Lo Russo A, Piemonte F, Mannucci L, Federici G . Rapid determination of mycophenolic acid in plasma by reversed-phase high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 776(2):251-4. DOI: 10.1016/s1570-0232(02)00353-7. View

Pulido J, Peyman G, Lesar T, Vernot J . Intravitreal toxicity of hydroxyacyclovir (BW-B759U), a new antiviral agent. Arch Ophthalmol. 1985; 103(6):840-1. DOI: 10.1001/archopht.1985.01050060100036. View

Gao H, Pennesi M, Qiao X, Iyer M, Wu S, Holz E . Intravitreal moxifloxacin: retinal safety study with electroretinography and histopathology in animal models. Invest Ophthalmol Vis Sci. 2006; 47(4):1606-11. DOI: 10.1167/iovs.05-0702. View

Watson D, Araya F, Galloway P, Beattie T . Development of a high pressure liquid chromatography method for the determination of mycophenolic acid and its glucuronide metabolite in small volumes of plasma from paediatric patients. J Pharm Biomed Anal. 2004; 35(1):87-92. DOI: 10.1016/j.jpba.2003.12.011. View

Fisher J, Lewis M, Blumenkranz M, Culbertson W, Flynn Jr H, CLARKSON J . The acute retinal necrosis syndrome. Part 1: Clinical manifestations. Ophthalmology. 1982; 89(12):1309-16. DOI: 10.1016/s0161-6420(82)34628-x. View

Hebert M, Lachapelle P, Dumont M . Reproducibility of electroretinograms recorded with DTL electrodes. Doc Ophthalmol. 1995; 91(4):333-42. DOI: 10.1007/BF01214651. View

Pulido J, Palacio M, Peyman G, Fiscella R, Greenberg D, Stelmack T . Toxicity of intravitreal antiviral drugs. Ophthalmic Surg. 1984; 15(8):666-9. View

Inan U, Avci B, Kusbeci T, Kaderli B, Avci R, Temel S . Preclinical safety evaluation of intravitreal injection of full-length humanized vascular endothelial growth factor antibody in rabbit eyes. Invest Ophthalmol Vis Sci. 2007; 48(4):1773-81. DOI: 10.1167/iovs.06-0828. View

Poirier J, Radembino N, Jaillon P . Determination of acyclovir in plasma by solid-phase extraction and column liquid chromatography. Ther Drug Monit. 1999; 21(1):129-33. DOI: 10.1097/00007691-199902000-00020. View

10.

Bahrami G, Mohammadi B . An isocratic high performance liquid chromatographic method for quantification of mycophenolic acid and its glucuronide metabolite in human serum using liquid-liquid extraction: application to human pharmacokinetic studies. Clin Chim Acta. 2006; 370(1-2):185-90. DOI: 10.1016/j.cca.2006.02.017. View

11.

Good S, de Miranda P . Metabolic disposition of acyclovir in the guinea pig, rabbit, and monkey. Am J Med. 1982; 73(1A):91-5. DOI: 10.1016/0002-9343(82)90071-7. View

12.

Marmor M, Fulton A, Holder G, Miyake Y, Brigell M, Bach M . ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol. 2008; 118(1):69-77. DOI: 10.1007/s10633-008-9155-4. View

13.

Rosenberry K, Bryan C, Sohn C . Acyclovir: evaluation of a new antiviral agent. Clin Pharm. 1982; 1(5):399-406. View

14.

Kim H, Csaky K, Chan C, Bungay P, Lutz R, Dedrick R . The pharmacokinetics of rituximab following an intravitreal injection. Exp Eye Res. 2005; 82(5):760-6. DOI: 10.1016/j.exer.2005.09.018. View

15.

Kim H, Csaky K, Gravlin L, Yuan P, Lutz R, Bungay P . Safety and pharmacokinetics of a preservative-free triamcinolone acetonide formulation for intravitreal administration. Retina. 2006; 26(5):523-30. DOI: 10.1097/00006982-200605000-00005. View

16.

Khoschsorur G, Erwa W . Liquid chromatographic method for simultaneous determination of mycophenolic acid and its phenol- and acylglucuronide metabolites in plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 799(2):355-60. DOI: 10.1016/j.jchromb.2003.10.074. View

17.

Marmor M, Holder G, Seeliger M, Yamamoto S . Standard for clinical electroretinography (2004 update). Doc Ophthalmol. 2004; 108(2):107-14. DOI: 10.1023/b:doop.0000036793.44912.45. View

18.

Brigden D, Whiteman P . The mechanism of action, pharmacokinetics and toxicity of acyclovir--a review. J Infect. 1983; 6(1 Suppl):3-9. DOI: 10.1016/s0163-4453(83)94041-0. View

19.

CRAPOTTA J, Freeman W, Feldman R, Lowder C, Ambler J, Parker C . Visual outcome in acute retinal necrosis. Retina. 1993; 13(3):208-13. DOI: 10.1097/00006982-199313030-00004. View

20.

Harazny J, Scholz M, Buder T, Lausen B, Kremers J . Electrophysiological deficits in the retina of the DBA/2J mouse. Doc Ophthalmol. 2009; 119(3):181-97. DOI: 10.1007/s10633-009-9194-5. View