Study of the effect of a number of natural and modified polysaccharides on the bioavailability and pharmacokinetic profile of nitazole when administered orally to rabbits
The pharmacokinetics of nitazole was studied after oral administration to rabbits in the form of a suspension or tablets together with a number of natural and modified polysaccharides. The obtained curves demonstrate a variety of pharmacokinetic profiles: for the suspension of nitazole with carboxymethyl starch, rapid absorption of nitazole is observed (Tmax=15 min), The concentration of nitazole in plasma is an order of magnitude higher than for suspension of nitazole with starch, the bioavailability of nitazole is 98 %, as with intravenous administration; for a suspension of nitazol with dialdehyde starch, rapid absorption of nitazole with Tmax = 1 hour is observed, gradual elimination with T0.5 = 7.4 hours, the retention time of nitazole in the body is MRT = 11.16 hours compared to 6 hours for starch, bioavailability was 83.7 %; for nitazol suspension with chitosan, the curve has the form of a plateau, Tmax = 7 hours, MRT = 10.16 hours. The bioavailability of nitazole with chitosan was 60.8 %; for a suspension of nitazol with alginate, the curve has Tmax = 2 hours and bioavailability of 57.3 %; the curve for nitazol tablets with alginate has Tmax = 6 hours and MRT = 6.49 hours, which is twice as much as for a suspension of nitazole with alginate. It was suggested that this is due to the transition of alginate in the acidic environment of the stomach into the water-insoluble alginic acid on the surface of the tablets, which prevents the release of nitazole from the tablets. It has been shown by methods of spin and fluorescent probes that, unlike starch and oxidized cellulose, sodium alginate is able to bind to macromolecules of serum bovine albumin and liposome membrane from phosphatidylcholine, displacing spin or fluorescent probes from the cavity of the SAB and lipid liposome membranes. The studied natural and modified polysaccharides can be used as excipients in drugs with controlled absorption.
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