Changes in the barrier mechanisms in the eye should determine the rational route for the administration and dosage of each drug in the treatment of traumatic injuries and other pathologies. The aim of this study was to examine the efficacy of intra-arterial delivery of 14C-riboflavin (as an “indicator”) and compare it with intravenous and intramuscular administration in an animal model of chemical eye burn. 14C-riboflavin (14C-I) was administered by intra-arterial (carotid artery), intravenous (femoral vein) and intramuscular (femoral muscle) routes. The total radioactivity was determined over 2 h in the plasma and structures of the rabbit’s eyes using a scintillation counter. The results of the study show that intravascular administration of 14C-I gives significantly higher concentrations of total radioactivity in the blood and is accompanied by a significant increase in the permeability of the blood-barrier and barrier in eyes suffering from burns. The highest concentration in the plasma and aqueous humour of the anterior chamber of the eye was observed during the first hour with the intra-arterial route of administration of 14C-I in either burnt and unburnt eyes. The distribution of total radioactivity in the structures of the eye over the 2 h of the experiment showed a higher level of the drug under intra-arterial administered in the uveal regions, namely: the iris, ciliary body, choroid, retina and also the sclera and cornea. This experimental model shows that intra-arterial administration can increase the bioavailability of a drug to the structures of the eye within a short period of time.
Żuk M, Sumriy SK, Zhuk OV. Elimination kinetics of synthetic interferon inducer tilorone in experimental animals. J Pre-Clin Clin Res. 2017; 11(2) 3 H]-I in rats and mice was studied following a single oral and intravenous administration. The excretion mass balance was monitored in the faeces and urine of rats and mice for 5 and 10 days, respectively. Radioactivity was determined in the samples of excreta using a liquid scintillation counter. Results. In rats, [3 H]-I were nearly fully (~80%) eliminated with excreta in 5 days, indicating a lack of any significant accumulation of the drug in the body. Faecal excretion of tilorone predominated (69.0% ± 2.8%), while the elimination in urine was less significant (9.8%8 ± 1.2%). A different pattern of elimination kinetics was observed in mice as excretion proceeded with equal efficiency in urine (27.85-28.9%) and faeces (26.45-24.4 %), regardless of the route of administration of the substance and at a substantially slower rate compared to rats: only 57.35-52.68% of total radioactivity was eliminated over 10 days following oral and intravenous administration of tilorone, respectively. MRT of tilorone in rats was 36 h and in mice 120-150 h. Conclusion. Parameters for the excretion of tilorone showed significant differences between the 2 groups of animals. Using the example of tilorone excretion kinetics validates the presented novel modified approach to determine the mean residence time (MRT) and amount of drug eliminated from the body during an infinitely long experimental period. This approach can be generally applied for interpretation of nonlinear elimination kinetics of xenobiotics.
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