Treatment of Cytomegalovirus Retinitis with Intravitreal Ganciclovir

Cantrill, Herbert L.; Henry, Keith; Melroe, N. Holly; Knobloch, William H.; Ramsay, Robert C.; Balfour, Henry H.

doi:10.1016/s0161-6420(89)32900-9

Cited by 166 publications

(39 citation statements)

References 31 publications

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“…[1][2][3][4] Therefore, GCV plays an important role in the treatment of ocular HSV and CMV infection. Because of its low lipophilicity, GCV showed poor ocular availability when topically applied.…”

Section: Introductionmentioning

confidence: 99%

Preparation and ocular pharmacokinetics of ganciclovir liposomes

Shen

2007

AAPS J

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Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The in vitro transcorneal permeability of GCV liposomes was found to be 3.9-fold higher than that of the solution. After in vivo instillation in albino rabbits, no difference was found in the precorneal elimination rate of GCV from liposome vs solution dosing. The aqueous humor concentration-time pro¿ les of both liposomes and solution were well described by 2-compartmental pharmacokinetics with ¿ rst-order absorption. The area under the curve of the aqueous humor concentration-time pro¿ les of GCV liposomes was found to be 1.7-fold higher than that of GCV solution. Ocular tissue distribution of GCV from liposomes was 2 to 10 times higher in the sclera, cornea, iris, lens, and vitreous humor when compared with those observed after solution dosing. These results suggested that liposomes may hold some promise in ocular GCV delivery.

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Section: Introductionmentioning

confidence: 99%

Preparation and ocular pharmacokinetics of ganciclovir liposomes

Shen

2007

AAPS J

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“…Other toxic effects include granulocytopenia, thrombocytopenia, azoospermia, and rise in the serum creatinine (Faulds and Heel, 1990). Relatively high systemic toxicity caused by intravenous therapy has lead to the intravitreal administration of GCV (Henry et al, 1987;Daikos et al, 1988;Ussery et al, 1988;Cantrill et al, 1989;Cochereau-Massin et al, 1991), which enabled considerable improvement and/or stabilization of HCMV retinitis in most (80 -100%) of the patients. Intravitreal administration has the advantage of maintaining high concentrations of the drug for effective control of ocular infections with minimal systemic adverse effects.…”

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confidence: 99%

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

Macha¹,

Mitra²

2002

Drug Metab Dispos

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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.

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“…The retinitis can be managed with systemic ganciclovir, but additional therapy may be given into the vitreous [42][43][44] .…”

Section: Management Of Cytomegalovirus Retinitismentioning

confidence: 99%

The eye in systemic sepsis

2002

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-Metastatic or endogenous endophthalmitis (EE) is a serious consequence of systemic sepsis. It is defined as intraocular infection resulting from haematogenous spread of organisms in which the initial focus of infection is at a site distal to the eye. A red/sore eye in a patient with a known septic focus needs urgent attention as EE can be a major cause of visual loss. Early diagnosis and treatment are associated with better visual outcome. This article focuses on the two main causes of EE, namely bacterial and fungal infections, and also briefly mentions dissemination of cytomegalovirus to the eye in immunocompromised patients. Although conscious patients may notice an ocular problem, unconscious or very sick patients may not; vigilance by medical staff in looking for early signs of this is extremely important.KEY WORDS: candida, ciprofloxacin, cytomegalovirus (CMV), endophthalmitis, floaters, hypopyon, red eye, retinal infiltrates, retinitis, septicaemia Endogenous fungal endophthalmitisFungal sepsis is identified most frequently in hospitalised patients who are seriously ill. Endogenous fungal endophthalmitis (EFE) occurs in 28-45% of patients with candidaemia 1,2,3 and is the most common form of endogenous endophthalmitis (EE) 4 . Patients usually present with floaters and decreased vision, unilateral or bilateral. Onset is often insidious; in its early stages EFE can be asymptomatic 2 , but if left untreated can have devastating consequences for visual function. Therefore, regular screening of high risk cases is undertaken in many centres 5,6 . High risk characteristics include those listed in Table 1. CandidiasisCandida albicans is the most common pathogen causing EFE and in some series is the causative agent in 85-99% of all cases 6,9 . Non-albicans candida spp are important as aetiological agents 10 because fungaemia with these species is associated with a higher incidence of endophthalmitis than with C. albicans 11 . Other causes of EFE in descending order of importance are Aspergillus fumigatus, cocciodioides, cryptococcus, fusarium, histoplasmosis and paecilomyces 4 .Diagnosis of ocular candidiasis. The clinical diagnosis of ocular candidiasis is largely made on the ocular appearance 8 . The organism typically causes inflammation in the choroid and retina, with subsequent spread into the vitreous cavity 8 . The ophthalmoscopic appearance is of one or more creamy-white, usually round and sometimes elevated retinal lesions, often sited in the posterior pole of the eye (Fig 1). They may vary in size from small pinpoint lesions to two-disc diameter in width 8 . If the vitreous is involved, multiple clumps may form ('puff balls') (Fig 2). Thread-like strands may connect these, producing a so-called 'string of pearls' appearance. Ocular lesions can indicate otherwise occult deep tissue fungal infection and are useful indicators of systemic candidiasis 12,13 . Although autopsy studies have demonstrated a high incidence (78%) of ocular involvement in patients with candidaemia 12 , the eye can be the ...

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Treatment of Cytomegalovirus Retinitis with Intravitreal Ganciclovir

Cited by 166 publications

References 31 publications

Preparation and ocular pharmacokinetics of ganciclovir liposomes

Preparation and ocular pharmacokinetics of ganciclovir liposomes

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

The eye in systemic sepsis

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