Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular

Abstract

As the need for nasal, ocular, spinal, and articular therapeutic compounds increases, toxicology assessments of drugs administered via these routes play an important role in human safety. This symposium outlined the local and systemic evaluation to support safety during the development of these drugs in nonclinical models with some case studies. Discussions included selection of appropriate species for the intended route; conducting nonclinical studies that closely mimic the intended use with adequate duration; functional assessment, if deemed necessary; evaluation of local tissues with special histological staining procedure; and evaluations of safety margins based on local and systemic toxicity.

Amniotic Suspension Allograft Modulates Inflammation in a Rat Pain Model of Osteoarthritis

“…At day 7, rats received an injection into the right knee with one of the following treatments (50 μl volume and n = 10 for all groups): saline (vehicle control), 25 μl ASA (25 μl ASA (ASA, ReNu®; Organogenesis, Birmingham, AL) + 25 μl saline), 50 μl ASA (no dilution), or 0.06 mg triamcinolone acetonide injectable suspension (Kenalog®‐10; Bristol Myers Squib, Princeton, NJ; positive control). The volume for dosing was established from a previously reported study with recommendations based on the body weight of rats . Behavioral testing was carried out at baseline and during the period following treatment; this schedule can be found in Table .…”

Models and Approaches Describing the Metabolism, Transport, and Toxicity of Drugs Administered by the Ocular Route

“…This apparent volume of distribution differs from the actual volume of the distribution since there is no evidence that cyclosporine is restricted to the eye. Recently, this error was acknowledged (Emami et al, 2018) and a direct measurement of vitreal volume in the monkey and other species has been made. The most reliable estimates of the vitreal volumes are now considered those reported by Covance (Covance: Comparison of ocular tissues weights (volumes) and tissue collection techniques in commonly used preclinical animal species.…”

Biokinetics and clearance of inhaled gold ultrasmall-in-nano architectures

“…It also has olfactory functions and protects the lungs by heating, humidifying and ltering the incoming airstream. 10 Interestingly, the nasal pathway offers an alternative route for the delivery to the brain, as therapeutics deposited onto the olfactory epithelium can directly translocate to the brain through the olfactory and trigeminal nerve pathways avoiding the strictly selective bloodbrain barrier (BBB) and minimizing systemic exposure. 3,10,11 In this study, the biokinetics, distribution, and clearance trends of gold ultrasmall-in-nano architectures (NAs) administered through a single intranasal application have been quantitatively evaluated.…”