Toxicity and Pharmacokinetics of Sustained-Release Dexamethasone in Beagle Dogs

Driscoll, Arthur; Blizzard, Charles D

doi:10.1007/s12325-015-0280-7

Cited by 13 publications

(13 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, no detectable ocular toxicity or IOP increase was observed with depot use. Previous preclinical examination of OTX-DP (the 0.4 mg depot) in this animal model has shown a lack of any systemic or ocular adverse effects with this depot, 10 providing further evidence that this dexamethasone depot is well tolerated in a preclinical model.…”

Section: Discussionsupporting

confidence: 57%

“…8 Initially developed for the treatment of dry eye, 9 punctum plugs have more recently demonstrated promise as intracanalicular depots, providing sustained drug delivery to the eye. 10 A dexamethasone-eluting depot called OTX-DP (DEXTENZA™; Ocular Therapeutix, Bedford, MA) has been developed and is currently under New Drug Application review with the US Food and Drug Administration (FDA) for the treatment of postoperative ocular pain, as well as in phase 3 clinical trials for the treatment of postoperative ocular inflammation and allergic conjunctivitis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic Studies of Sustained-Release Depot of Dexamethasone in Beagle Dogs

Blizzard¹,

Desai²,

Driscoll³

2016

Journal of Ocular Pharmacology and Therapeutics

Self Cite

View full text Add to dashboard Cite

Purpose: To examine the pharmacokinetic characteristics of sustained-release dexamethasone depots in two separate canine studies.Methods: Dexamethasone depots loaded with a clinically representative (0.4 mg) dose (DEXTENZA™; Ocular Therapeutix) or an elevated (0.7 mg) dose were inserted into the canaliculi of beagle eyes (n = 37 and n = 34, respectively). Tear fluid was collected for pharmacokinetic analysis of dexamethasone in both studies at predetermined time points. Explanted 0.4 mg depots were collected weekly to measure remaining drug level. Clinical observations and ophthalmic examinations were performed in both studies at each visit.Results: The 0.4 mg depots released a median 308 μg by day 15 and tapered to complete drug release by day 28. Median dexamethasone tear fluid concentrations in the 0.4 mg study group decreased from 2,805 ng/mL at day 7 to 0 ng/mL on day 28. Median dexamethasone tear fluid concentrations in the 0.7 mg study group decreased from 4,370 ng/mL at 6 h post insertion to 830 ng/mL on day 35. Mean ± standard deviation intraocular pressures in the 0.4 and 0.7 mg study groups were 20.7 ± 2.8 and 19.0 ± 4.1 mmHg at baseline, respectively, and demonstrated no meaningful change (20.5 ± 3.0 and 20.6 ± 2.9 mmHg, respectively) over the studies' durations. No ocular toxicities were attributed to the dexamethasone depot.Conclusion: Sustained-release dexamethasone produced no identifiable ocular toxicity in this animal model, and pharmacokinetics demonstrated a sustained and tapered drug release over 28 days at a 0.4 mg dose and exceeded 35 days at a 0.7 mg dose.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Studies of Sustained-Release Depot of Dexamethasone in Beagle Dogs

Blizzard¹,

Desai²,

Driscoll³

2016

Journal of Ocular Pharmacology and Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…26,27 These depot systems provide not only drug delivery over a desired period of time, but can also taper in concentration as we might in clinical practice if utilizing topical eye drops. 28 Sustained-release drug delivery systems therefore have the potential to minimize or negate the impact of medication non-compliance or improper instillation by reducing or eliminating the burden of an eye drop regimen, while still controlling post-operative inflammation.…”

Section: Introductionmentioning

confidence: 99%

<p>Dexamethasone 0.4mg Sustained-Release Intracanalicular Insert in the Management of Ocular Inflammation and Pain Following Ophthalmic Surgery: Design, Development and Place in Therapy</p>

Brooks

Jabbehdari

Gupta

2020

OPTH

View full text Add to dashboard Cite

Inflammation and pain are two prevalent findings after ocular surgery. Corticosteroids are widely administrated as a core treatment to control post-surgical inflammation and pain. Improper patient adherence to post-operative eye drop regimens, limited bioavailability of topical eye drops, and the negative impact of preservatives used in many of these eye drops, has made a strong case for novel therapies in the treatment of post-operative pain and inflammation. This review of the literature will focus on the role of intracanalicular sustained-release dexamethasone (Dextenza, Ocular Therapeutix, Bedford, MA, USA) for the management of ocular inflammation and pain.

show abstract

“…Unfortunately, the device was not superior to timolol in a Phase IIB human clinical trial and also did not achieve its primary end point in a Phase III human clinical trial, even though it was redesigned 66 . Additionally, it is likely that any device designed for implantation into the human inferior canaliculus would need to be modified for dogs as the human nasolacrimal puncta are reportedly 0.2 to 0.5 mm in diameter 67,68 but in a study of 100 dogs where inferior (ventral) nasolacrimal punctal diameter was measured using a punctal gauge, 89.5% of dogs of varying body weights fell between 0.6 and 0.8 mm 69 . Furthermore, 6/24 dogs weighing >30 kg had puncta >0.8 mm diameter 69 .…”

Section: Prostaglandin Devicesmentioning

confidence: 99%

Medical anti‐glaucoma therapy: Beyond the drop

Miller

Eaton

2020

Veterinary Ophthalmology

View full text Add to dashboard Cite

Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to prescribed anti‐glaucoma drop regimens. In an effort to circumvent these challenges, a number of new anti‐glaucoma therapies with sustained effects have emerged. Methods for sustained delivery of prostaglandin analogs are being intensely investigated and many are in human clinical trials. Intracameral devices include the following: Allergan's Durysta™ Bimatoprost SR, Envisia Therapeutics’ ENV515 travoprost implant, Glaukos’ iDose™, Ocular Therapeutix's OTX‐TIC travoprost implant, and Santen's polycaprolactone implant with PGE2‐derivative DE‐117. Other prostaglandin‐based technologies include Allergan's bimatoprost ring (placed in the conjunctival fornix), Ocular Therapeutics’ OTX‐TP intracanalicular travoprost implant, subconjunctival latanoprost in a liposomal formulation, and the PGE2 derivative PGN 9856‐isopropyl ester that is applied to the periorbital skin. Exciting breakthroughs in gene therapy include using viral vectors to correct defective genes such as MYOC or to modulate gonioimplant fibrosis, CRISPR technology to edit MYOC or to alter aquaporin to reduce aqueous humor production, and siRNA technology to silence specific genes. Stem cell technology can repopulate depleted tissues or, in the case of Neurotech's Renexus® NT‐501 intravitreal implant, serve as a living drug delivery device that continuously secretes neurotrophic factors. Other unique approaches involve nanotechnology, nasal sprays that deliver drug directly to the optic nerve and noninvasive alternating current stimulation of surviving cells in the optic nerve. Over time these modalities are likely to challenge the preeminent role that drops currently play in the medical treatment of glaucoma in animals.

show abstract

Toxicity and Pharmacokinetics of Sustained-Release Dexamethasone in Beagle Dogs

Abstract: Ocular Therapeutix.

Cited by 13 publications

References 10 publications

Pharmacokinetic Studies of Sustained-Release Depot of Dexamethasone in Beagle Dogs

Pharmacokinetic Studies of Sustained-Release Depot of Dexamethasone in Beagle Dogs

<p>Dexamethasone 0.4mg Sustained-Release Intracanalicular Insert in the Management of Ocular Inflammation and Pain Following Ophthalmic Surgery: Design, Development and Place in Therapy</p>

Medical anti‐glaucoma therapy: Beyond the drop

Contact Info

Product

Resources

About