Impact of silicone oil tamponade on intravitreally injected vancomycin pharmacokinetics in cynomolgus monkey eyes

Hira, Daiki; Kitagawa, Tomoya; Imamura, Taku; Kakinoki, Masashi; Ueshima, Satoshi; Okano, Tomonobu; Ohji, Masahito; Kakumoto, Mikio; Takato, Tsuyoshi

doi:10.1016/j.ijpharm.2021.121185

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…Vancomycin, as by far the drug with the highest molecular weight and the only peptide therapeutic studied in our experiments, showed a drop below the expected concentrations starting 3 h after application, indicating a higher concentration in the vitreous body compared to the aqueous phase, while both voriconazole and ceftazidime equally dissolved in the vitreous and the aqueous phase. Again, these results are in line with Hira et al [ 10 ]. The authors showed that, in vitrectomized monkey eyes compared to eyes with the vitreous body still present, vancomycin is cleared at faster rates, which is possibly caused by the loss of otherwise protein-bound vancomycin that could be slowly released.…”

Section: Discussionsupporting

confidence: 93%

“…In line with the data present in our study, levels of both drugs were highly elevated in the aqueous phase harvested from the anterior chamber of the eye after certain time points. As Hira et al [ 10 ] point out in their computational model of the pharmacokinetics for both vancomycin and ceftazidime and Leung et al [ 18 ] in their experimental laboratory study of vancomycin, these elevated levels are most likely caused by the decrease in the volume of distribution in the silicone-oil-filled eye due to the decreased solubility of the drugs in silicone oil compared to the natural vitreous body.…”

Section: Discussionmentioning

confidence: 99%

“…Focusing on anti-infectious drugs, commonly administered drugs show a broad spectrum of lipophilicity and size, ranging from the hydrophilic large glycopeptide antibiotic vancomycin to the lipophilic antifungal agent voriconazole. Few studies have proven the changes in the distribution, concentration and elimination of ceftazidime and vancomycin in a low number of macaque eyes filled with lighter-than-water silicone oil compared to regular eyes with intact vitreous bodies [ 9 , 10 ]. However, no data regarding whether these alterations also hold true in eyes filled with heavier-than-water silicone oils are available.…”

Section: Introductionmentioning

confidence: 99%

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Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body

et al. 2022

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Silicone oil endotamponades provide a reservoir for drugs in the eye. Following vitrectomy surgery to treat retinal detachments, extensive diabetic retinopathy or endophthalmitis, they can be used as long-term lipophilic depots. This study aimed to investigate the physicochemical properties of intravitreally applied drugs of different lipophilicity, namely vancomycin, ceftazidime and voriconazole. For this purpose, an in vitro model of the silicone-oil-filled eye compared to porcine vitreous bodies (PVBs) was used. In a glass container, either light or heavy silicone oil or PVB was set into equilibrium with an aqueous fluid. Vancomycin, voriconazole and ceftazidime were added in concentrations commonly applied in clinical practice. The time course of the concentration of the drugs was determined in the hydrophilic phase for up to 24 h. With silicone oil present, the concentrations of vancomycin, voriconazole and ceftazidime were elevated in the aqueous humor when compared to the vitreous body (p < 0.001 for all drugs). With increasing lipophilicity, higher concentrations of the drug dissolved in silicone oil after 24 h (52.7%, 49.1% and 34.3% for vancomycin, ceftazidime and voriconazole, respectively). While no difference between lighter- and heavier-than-water silicone oil was apparent for vancomycin and ceftazidime (p = 0.17 and p = 0.72), voriconazole dissolved significantly better in the heavier-than-water silicone oil (p = 0.002). A higher-than-expected percentage of the glycopeptide vancomycin dissolved in the porcine vitreous body, possibly due to protein binding. In conclusion, silicone oils influence the drug concentration and distribution of intravitreally applied drugs depending on their lipophilicity. The addition of F6H8 used to create heavy silicone oils attenuates these effects for lipophilic drugs. Knowledge of the distribution of these intravitreally applied drugs is crucial to ensure the desired anti-infectious effect.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body

et al. 2022

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Evidence-based guidelines for drug dosing in intravitreal injections in silicone oil-filled eyes: Pharmacokinetics, safety, and optimal dosage

Ferro Desideri,

Sim,

Bernardi

et al. 2025

Survey of Ophthalmology

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In Vitro Physicochemical and Pharmacokinetic Properties of Bevacizumab Dissolved in Silicone Oils Compared to Hydrogel-Substitutes and Porcine Vitreous Bodies

Hammer,

Herth,

Herbster

et al. 2024

Gels

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Anti-VEGF agents, e.g., bevacizumab, are used in retinal surgery, while their interaction with silicone oils and novel hydrogels remains unclear. This study examines the in vitro pharmacokinetics of bevacizumab in silicone oil-filled eyes compared to various hydrogel replacements and the porcine vitreous body as well as its impact on the interface tension of silicone oils. An in vitro model filled with light or heavy silicone oil, porcine vitreous bodies, or hydrogels (alginate and polyethylene glycol (PEG)-based) was equilibrated with a balanced salt solution. Monitoring of bevacizumab in the aqueous phase was conducted for up to 24 h, and its effect on interfacial tension was studied. Significant differences in bevacizumab partitioning were observed across endotamponades after 24 h. In silicone oils, bevacizumab was found exclusively in the aqueous phase, while in the other endotamponades, it accumulated in the gel phase (96.1% in porcine vitreous body, 83.5% in alginate, and 27.6% in PEG-based hydrogel). Bevacizumab significantly reduced interfacial tension (40 to 8 mN/m), possibly enhancing silicone oil emulsification. The type of endotamponade heavily influenced the bevacizumab concentration in the aqueous. The vitreous body and replacement hydrogels likely serve as a drug reservoir, highlighting the need for in vivo studies to explore these interactions prior to clinical application.

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Impact of silicone oil tamponade on intravitreally injected vancomycin pharmacokinetics in cynomolgus monkey eyes

Cited by 3 publications

References 31 publications

Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body

Intravitreal Application: Physicochemical Properties of Drugs Dissolved in Silicone Oils of Different Density in Comparison to the Porcine Vitreous Body

Evidence-based guidelines for drug dosing in intravitreal injections in silicone oil-filled eyes: Pharmacokinetics, safety, and optimal dosage

In Vitro Physicochemical and Pharmacokinetic Properties of Bevacizumab Dissolved in Silicone Oils Compared to Hydrogel-Substitutes and Porcine Vitreous Bodies

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