HPLC–MS/MS studies of brimonidine in rabbit aqueous humor by microdialysis

Aim: The pharmacokinetic study of the brimonidine tartrate in situ gel in the anterior chamber of the rabbit eye was studied by microdialysis technique, and samples were analyzed by HPLC–MS/MS. Materials & methods: It was monitored in ESI mode at transition 291.9→212.0 and 296.0→216.0 for brimonidine and internal standard, respectively. Acetonitrile and 0.1% aqueous formic acid (50:50, v/v) were used as the mobile phase at 0.4 ml/min. Results & conclusion: It showed a good linear correlation between 5 and 5000 ng/ml in microdialysis solution, and the inter- and intra-day precision (relative standard deviation) was less than 4.0%. The pharmacokinetic study showed that the AUC(0-t) of in situ gel was 3.5-times than that of eyedrops, which significantly improve the bioavailability of brimonidine.

Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 1. THR-149

Intravitreal (IVT) injection of pharmacological agents is an established and widely used procedure for the treatment of many posterior segment of the eye diseases. IVT injections permit drugs to reach high concentrations in the retina whilst limiting systemic exposure. Beyond the risk of secondary complications such as intraocular infection, the potential of systemic adverse events cannot be neglected. Therefore, a detailed understanding of the rules governing systemic exposure following IVT drug administration remains a prerequisite for the evaluation and development of new pharmacological agents intended for eye delivery. We present here a novel mathematical model to describe and predict circulating drug levels following IVT in the rabbit eye, a species which is widely used for drug delivery, pharmacokinetic, and pharmacodynamic studies. The mathematical expression was derived from a pharmacokinetic model that assumes the existence of a compartment between the vitreous humor compartment itself and the systemic compartment. We show that the model accurately describes circulating levels of THR-149, a plasma kallikrein inhibitor in development for the treatment of diabetic macular edema. We hypothesize that the model based on the rabbit eye has broader relevance to the human eye and can be used to analyze systemic exposure of a variety of drugs delivered in the eye.

Quantitative Evaluation of the Supercontinuum Laser Eye Dazzling Effect: in vivo Experimental Research

Background: Laser eye dazzling affects the visual performance through the instant high-intensity light stimulation. The temporary loss or deterioration of the visual function may occur when radiated by lasers. To quantitatively evaluate the dazzling effect of each spectrum band of supercontinuum laser, we conducted an experimental research for exploring the safety and dazzling of animals’ eyes. Methods: Under the condition of dark adaption, the laser with different power densities and spectral bands was output, and the rabbit eyes were radiated by normal incident mode for 0.25 s. The fundus of the rabbit eyes was examined through the inspection mirror, and the upper limit of safe power density was explored. Rabbit eyes were radiated at the upper limit of safe power density, and the microscopic damage model was established for pathomorphological analysis. The eyes were radiated with blinding light for 0.1 s. The visual electrophysiological signals were collected dynamically and the recovery time of ERG-b amplitude was recorded and analyzed after laser radiation. Results: Under dark adaptation, the upper limit of safe power density was 247.00 mW/cm2 in the VS, 194.00 mW/cm2 in the VIS, 1184.00 mW/cm2 in the IS, and 1052.00 mW/cm2 in the FS. The above power densities of laser radiation in rabbit eyes could cause pathological changes of retinal structure, such as local bulge, uneven thickness and disorder of inner and outer nuclear layers, local inflammatory exudation and so on. When the power density was 8.00 mW/cm2, the recovery time of ERG-b wave in rabbit eye was 4.11 ± 0.67 s. When the power density was 12.00 mW/cm2, the recovery time of ERG-b wave in rabbit eye was 4.16 ± 0.55 s. The recovery time of ERG-b wave was 4.50 ± 0.94 s at the power density of 4.60 mW/cm2 in the full spectrum-1, 3.81 ± 0.11 s at the power density of 5.00 mW/cm2 in the full spectrum-2, and 628.00 mW/cm2 in the infrared spectrum. The recovery time of ERG-b wave was only 0.84 ± 0.09 s. Conclusion: The VS, FS, FS-1 and FS-2 of the supercontinuum laser had a good dazzling effect on rabbit eyes, and the dazzling effect was enhanced with the increase of radiation power density, but the infrared spectrum had a little dazzling effect.

Parameters of acute and chronic toxicity of the insecticidal preparation VEIS-2

The main safety indicators of the new preparation VEIS-2, containing natural or chemically modified avermectins as an active ingredient, when exposed to the skin of mammals, intended to protect the downy feather raw material from keratophagous insects, have been studied. It has been established that the VEIS-2 compositions containing abamectin or avermectin B1a hemisuccinate as an active principle have a mild irritating effect on the conjunctival mucosa of the rabbit eye. With single and multiple applications on the skin, the above compositions do not cause such functional and structural changes in the skin as edema, erythema, cracks, desquamation. The presence of skin-resorptive and allergenic action in the compositions of the VEIS-2 preparation with abamectin or hemisuccinate avermectin B1a using the "test tube method" in rats, as well as using the reaction of specific lysis of leukocytes (RSLL), has not been established. It was shown that the VEIS-2 composition based on avermectin complex has a more pronounced local irritant effect on laboratory animals in terms of toxicity and allergenicity.