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.
Introduction The low serum concentration of the anti-tuberculosis (TB) drugs in TB patients is observed quite often, but the significance of this phenomenon remains controversial. Aim The aim of the presented research was to clarify the association between isoniazid concentration and TB-treatment outcomes. Material and methods Blood samples were obtained from 86 patients with newly diagnosed pulmonary TB at Odessa Regional TB Hospital in 2015. The level of isoniazid in blood was measured 2 h, 4 h, 6 h, and 24 h after the administration of isoniazid. The medical records of the enrolled patients at the beginning and at the end of the in-patient treatment, and the activity of the biochemical indices were considered. Results and discussion At the end of the in-patient treatment in patients with a serum isoniazid concentration of more than 2 µg/mL (HIC), 4 h after the drug administration, the resorption of TB infiltrates in lungs occurred 1.3 times more frequently than in patients with an isoniazid concentration of less than 2 µg/mL (LIC). According to the culture method, the smear conversion occurred 3.1 times more often in patients with HIC than in the LIC ones. A positive correlation was found between the isoniazid serum level with the bilirubin level, thymol probe, and the AsAT activity, which proved the higher risk of hepatotoxicity in patients with HIC. Conclusions Thus, the measurement of the isoniazid concentration after 4 h of isoniazid administration can predict the outcome of the TB-treatment. It is postulated that the recommended concentration of isoniazid in blood 4 h after its administration > 2 µg/mL.
Among the factors that can influence the course and effectiveness of the treatment of pulmonary tuberculosis (TB) the genetic characteristics of patients play an important role. It is established that cytochrome (CYP) 3A4/5 is involved in metabolism of more than 30 % of xenobiotics. Consequently, the activity of this enzyme is greatly influenced by responsible genes, such as CYP3А4. The aim of the study was the investigation of prognostic value of CYP3A4 polymorphism on the course and effectiveness of anti-tuberculosis therapy in patients with pulmonary TB. Materials and methods. Using PCR method, a detection of polymorphism of CYP3A4*1B, CYP3A4*1G genes, which determine the activity of CYP3A4 enzyme, was performed in 105 patients with newly diagnosed pulmonary TB. We have revied medical records at the beginning and at the end of inpatient treatment and considered the form, extent, regression rate of TB-lesions, and the rate of smear-positive cases. A statistical analysis of study data, expressed in absolute or relative values, was done using Pearson’s chi-squared test. Results: It was established that out of 105 enrolled TB-patients 84 individuals (80,0%) carried the genotype of “rapid metabolizers” (RA), the rest – 15 (14,3%) and 6 (5,7%) individuals were “intermediate metabolizers” (IM) and “slow metabolizers” (SM) correspondently. According to CYP3A4 genotype in patients with SM and IM the bi-lateral lesions as well as the processes of pulmonary destruction and dissemination, as well as smearpositiveness occurred more frequently than in RM. For example, in IM group the dissemination was observed almost two times more frequently than in RM (Р<0,05; χ2=4,44). At the end of the in-patient treatment in SM remaining TB-infiltrates observed more often, while the resolution of consolidation registered more rarely (66,7%) than in IM and RM (81,0% and 80,0%, correspondently). Also, in SM the TB infiltrates remained more often than in RM (33,3% versus 8,3%, Р<0,05; χ2=4,44). At the same time in IM the smear-positive status remained more often than in other groups. Conclusion. Genotypes of “intermediate metabolizers” and “slow metabolizers” according to CYP3A4 genes were associated with unfavorable pulmonary disease both at initiation and at the end of in-patient phase of the TB treatment. Identification of CYP3A4 genotype in pulmonary TB patients allows allocation of the groups of high risk of unfavorable TB course. Key words: pulmonary tuberculo
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