Intravitreal Ganciclovir Pharmacokinetics in Rabbits and Man

Ashton, Paul; Brown, Joel D.; Pearson, P. Andrew; Blandford, D L; Smith, Thomas J.; Anand, Rajiv; Nightingale, Steven; Sanborn, George E.

doi:10.1089/jop.1992.8.343

Cited by 28 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical trials reported good response rates to intravitreal induction therapy with GCV (Cochereau-Massin et al, 1991). However, very few studies have been carried out to date delineating the intravitreal pharmacokinetics of GCV (Henry et al, 1987;Ashton et al, 1992;Morlet et al, 1996). The major constraint to the development and assessment of posterior segment pharmacokinetics of drugs in animal models is the inaccessibility of the ocular fluids for continuous serial sampling.…”

mentioning

confidence: 99%

Ocular Disposition of Ganciclovir and Its Monoester Prodrugs following Intravitreal Administration Using Microdialysis

Macha¹,

Mitra²

2002

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:The present study was carried out to delineate the ocular pharmacokinetics of ganciclovir (GCV) following intravitreal administration. Another objective was to achieve sustained therapeutic concentrations of GCV in the vitreous over a prolonged period of time using its acyl monoester prodrugs (acetate, propionate, butyrate, and valerate). New Zealand albino male rabbits (2-2.5 kg) were kept under anesthesia. A concentric microdialysis probe was implanted in the vitreous using a 21-guage needle, and a linear microdialysis probe was implanted in the anterior chamber across the cornea using a 25-guage needle. The probes were perfused with isotonic phosphate buffer saline (pH 7.4) at a flow rate of 2 l/min. The drugs were administered (0.2 moles) intravitreally and the samples were collected every 20 min over a period of 10 h. The vitreal terminal elimination half-life (t 1/2 ␤) of GCV was found to be 426 ؎ 109 min. The hydrolysis rate and vitreal clearance of the prodrugs increased with the ascending ester chain length. The vitreal elimination half-lives (t 1/2k10 ) of GCV, acetate, propionate, butyrate, and valerate esters of GCV were 170 ؎ 37, 117 ؎ 50, 122 ؎ 13, 55 ؎ 26, and 107 ؎ 14 min, respectively. A parabolic relationship was observed between the vitreal elimination rate constant and the ester chain length. Mean residence time (MRT) of the regenerated GCV following prodrug administration was found to be three to four times the value obtained after GCV injection. In conclusion, these studies have shown that the ester prodrugs generated therapeutic concentrations of GCV in vivo, and the MRT of GCV could be enhanced by 3-to 4-fold through prodrug modification.

show abstract

mentioning

confidence: 99%

Ocular Disposition of Ganciclovir and Its Monoester Prodrugs following Intravitreal Administration Using Microdialysis

Macha¹,

Mitra²

2002

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…It is contraindicated in patients with hypersensitivity to ganciclovir or acyclovir and in those with active bacterial, mycobacterial, and fungal eye infections and severe thrombocytopenia. [9][10][11] In a phase III trial of 188 AIDS subjects with newly diagnosed CMV retinitis, Martin et al demonstrated that the time to disease progression was significantly delayed (216 days) in patients who received Vitrasert compared with those on intravenous ganciclovir treatment (104 days). 12 However, more recent studies suggest that, in the era of highly active antiretroviral therapy, a ganciclovir implant device is less effective than systemic therapy at decreasing disease dissemination and improving patient survival.…”

Section: Intraocular/intravitreal Implantsmentioning

confidence: 99%

Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development

Bansal

Garg²,

Sharma

et al. 2016

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Ocular drug delivery by conventional routes of administration does not maintain therapeutic drug concentrations in the target tissues for a long duration because of various anatomical and physiological barriers. Treatment of diseases of the posterior segment of the eye requires novel drug delivery systems that can overcome these barriers for efficacious delivery, provide controlled release for the treatment of chronic diseases, and increase patient's and doctor's convenience to reduce the dosing frequency and associated side effects. Thereby, an increasing number of sustained-release drug delivery devices using different mechanisms have been developed. This article discusses various current and future sustained-release drug delivery systems for the posterior segment disorders.

show abstract

“…Among these most promising developments are intravitreal drug delivery devices designed to deliver drugs with precision directly to the vitreous, retina, and choroid. 74,75 Intravitreal Implantable Device Technology Implantable sustained-release intravitreal device technology has being given much impetus due to the perceptible benefits afforded over the use of topical eye-drops, systemic drug administration and direct intravitreal injections as modes of drug delivery to the posterior segment of the eye as described earlier. 64,76 Solid biocompatible implantable devices for sustained or controlled intravitreal drug delivery to the posterior segment of the eye have been developed employing diverse approaches and includes the use of implantable devices such as osmotic mini-pumps, nonbioerodible and bioerodible drug-loaded pellets, configured capillary fibers, biodegradable scleral plugs, scleral discs, polymeric matrices and scaffolds of various geometries providing unique mechanisms of drug release for the delivery of drugs to the posterior segment of the eye.…”

Section: The Blood-ocular Barriers: An Impediment To Intraocular Drugmentioning

confidence: 99%

A review of implantable intravitreal drug delivery technologies for the treatment of posterior segment eye diseases

Choonara

Pillay

Danckwerts

et al. 2010

Journal of Pharmaceutical Sciences

120

View full text Add to dashboard Cite

Intravitreal Ganciclovir Pharmacokinetics in Rabbits and Man

Cited by 28 publications

References 5 publications

Ocular Disposition of Ganciclovir and Its Monoester Prodrugs following Intravitreal Administration Using Microdialysis

Ocular Disposition of Ganciclovir and Its Monoester Prodrugs following Intravitreal Administration Using Microdialysis

Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development

A review of implantable intravitreal drug delivery technologies for the treatment of posterior segment eye diseases

Contact Info

Product

Resources

About