Browsing by Subject "Rabbit"
Now showing items 1-7 of 7
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(2022)Quantitation of ocular drug metabolism is important, but only sparse data is currently available. Herein, the pharmacokinetics of four drugs, substrates of metabolizing enzymes, was investigated in albino rabbit eyes after intracameral and intravitreal administrations. Acetaminophen, brimonidine, cefuroxime axetil, and sunitinib and their corresponding metabolites were quantitated in the cornea, iris-ciliary body, aqueous humor, lens, vitreous humor, and neural retina with LC-MS/MS analytics. Non-compartmental analysis was employed to estimate the pharmacokinetic parameters of the parent drugs and metabolites. The area under the curve (AUC) values of metabolites were 12-70 times lower than the AUC values of the parent drugs in the tissues with the highest enzymatic activity. The ester prodrug cefuroxime axetil was an exception because it was efficiently and quantitatively converted to cefuroxime in the ocular tissues. In contrast to the liver, sulfotransferases, aldehyde oxidase, and cytochrome P450 3A activities were low in the eye and they had negligible impact on ocular drug clearance. With the exception of esterase substrates, metabolism seems to be a minor player in ocular pharmacokinetics. However, metabolites might contribute to ocular toxicity, and drug metabolism in various eye tissues should be investigated and understood thoroughly.
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(2021)Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUCiris-ciliary body than AUCaqueous humor, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.
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(2022)Background: Earlier studies indicate that the risk for uterine tumours in rabbits may be as high as 60-80%. This high occurrence and the need for routine neutering of non-breeding pet rabbits have recently been in the spotlight. Methods: This study aimed to describe and compare macroscopic and histopathological alterations in uteri collected from domestic rabbits of various ages neutered, deceased, or euthanized without a suspected uterine disorder (NoUD; n = 94) and from rabbits with a suspected uterine disorder (UD; n = 22). Results: In the NoUD group, uteri of 41 rabbits (44%) displayed histopathological findings and 12 rabbits (13%) had neoplasms. Samples from thirteen rabbits (14%) evinced histopathological findings with no macroscopic alterations. The most frequent diagnoses were cystic endometrial hyperplasia (26% of the 41 uteri), adenocarcinoma (9%), and polyps (5%). In the UD group, uteri from 21 (95%) out of 22 rabbits exhibited pathological alterations; in 2 (10%) of these, the changes (cystic endometrial hyperplasias) were seen only in histology. The most frequent diagnoses in the uteri of the UD group were cystic endometrial hyperplasia (77%) and adenocarcinoma (54%). Uterine malignant neoplasia affected 40% of all rabbits aged over 3 years, and the odds of a malignant uterine tumour in these rabbits were approximately 19-fold higher than in rabbits aged under 3 years. Conclusions and clinical relevance: Uterine disorders are common in domestic rabbits, even without a suspected uterine disease, and the risk of uterine neoplasia markedly increases after 3 years of age. A macroscopically normal uterus may have pathological changes and ovariohysterectomy should be therefore preferred over ovariectomy at least in older rabbits.
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(2015)Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics. (C) 2015 The Authors. Published by Elsevier Ltd.
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(2020)Background Vitamin D deficiency and related metabolic bone diseases in pet rabbits have been intermittently debated. In human research, the parathyroid hormone concentration in relation to the 25-hydroxyvitamin D concentration is used to determine vitamin D deficiency. Thus, this study aimed to identify the breakpoint in the 25-hydroxyvitamin D concentration indicating a significant change in the parathyroid hormone concentration in 139 pet rabbits. An enzyme immunoassay kit was used for 25-hydroxyvitamin D analysis and the intact parathyroid hormone (PTH 1-84) immunoradiometric assay kit for parathyroid hormone analysis. The mid-tibial cortical bone density was measured using peripheral quantitative computed tomography. A segmented linear regression analysis was performed, with the 25-hydroxyvitamin D concentration as the independent variable, and parathyroid hormone, ionised calcium, total calcium, inorganic phosphorus concentrations and the mid-tibial cortical density as the dependent variables. Results The breakpoint for the parathyroid hormone concentration occurred at a 25(OH)D concentration of 17 ng/mL, whereas the cortical bone density breakpoint occurred at a 25-hydroxyvitamin D concentration of 19 ng/mL. No breakpoints were found for ionised calcium, total calcium or phosphorus. Conclusions These results suggest that a serum 25-hydroxyvitamin D concentration of 17 ng/mL serves as the threshold for vitamin D deficiency in rabbits. Nearly one-third of the rabbits had a serum 25-hydroxyvitamin D concentration below this threshold. Concerns persist regarding the high prevalence of vitamin D deficiency in pet rabbits and the possible health consequences caused by a chronic vitamin D deficiency, including the risk for metabolic bone diseases.
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(BioMed Central, 2020)Abstract Background Vitamin D deficiency and related metabolic bone diseases in pet rabbits have been intermittently debated. In human research, the parathyroid hormone concentration in relation to the 25-hydroxyvitamin D concentration is used to determine vitamin D deficiency. Thus, this study aimed to identify the breakpoint in the 25-hydroxyvitamin D concentration indicating a significant change in the parathyroid hormone concentration in 139 pet rabbits. An enzyme immunoassay kit was used for 25-hydroxyvitamin D analysis and the intact parathyroid hormone (PTH 1–84) immunoradiometric assay kit for parathyroid hormone analysis. The mid-tibial cortical bone density was measured using peripheral quantitative computed tomography. A segmented linear regression analysis was performed, with the 25-hydroxyvitamin D concentration as the independent variable, and parathyroid hormone, ionised calcium, total calcium, inorganic phosphorus concentrations and the mid-tibial cortical density as the dependent variables. Results The breakpoint for the parathyroid hormone concentration occurred at a 25(OH)D concentration of 17 ng/mL, whereas the cortical bone density breakpoint occurred at a 25-hydroxyvitamin D concentration of 19 ng/mL. No breakpoints were found for ionised calcium, total calcium or phosphorus. Conclusions These results suggest that a serum 25-hydroxyvitamin D concentration of 17 ng/mL serves as the threshold for vitamin D deficiency in rabbits. Nearly one-third of the rabbits had a serum 25-hydroxyvitamin D concentration below this threshold. Concerns persist regarding the high prevalence of vitamin D deficiency in pet rabbits and the possible health consequences caused by a chronic vitamin D deficiency, including the risk for metabolic bone diseases.
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(2020)Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics of a cocktail of three beta blockers after their topical administration into the albino rabbit eye. Samples from aqueous humour were analysed with LC-MS/MS. The pharmacokinetic parameters were estimated using compartmental and non-compartmental analyses. The ocular bioavailability was covering broad range of values: atenolol (0.07 %), timolol (1.22%, 1.51%) and betaxolol (3.82%, 4.31%). Absolute ocular bioavailability presented a positive trend with lipophilicity and the values showed approximately 60-fold range. The generated data enhances our understanding for ocular pharmacokinetics of drugs and may be utilized in pharmacokinetic model building in ophthalmic drug development.
