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Slow penetration of [3H] tiazofurin into guinea pig brain by a saturable mechanism.

The aim of this study was to investigate the transport of tiazofurin (2-beta-D-ribofuranosyl thiazole-4-carboxamide) across the blood-brain barrier (BBB) using brain vascular perfusion and capillary depletion method in the guinea pig. Values for volume of distribution of [3H] tiazofurin in brain increased slowly and almost linearly in time, from 1% of its plasma concentration at 1 min to 5% after 15 min of perfusion. Unidirectional transport constant Kin was 2.61 +/- 0.21 x 10(-3) ml/min/g. According to these results, it is evident that tiazofurin slowly penetrates the BBB. Addition of unlabeled tiazofurin to the perfusing medium caused a significant decrease in the uptake of [3H] labeled tiazofurin (Kin = 0.77 +/- 0.1 x 10(-3) ml/min/g). Therefore, penetration of tiazofurin from blood into brain seems to be a saturable process. Presence of potential inhibitors of tiazofurin blood-to-brain transport (adenosine and dipyridamole) did not cause complete inhibition of tiazofurin brain uptake. Thus, it could be assumed that transport of tiazofurin from blood into brain is only partially mediated by the nucleosides transport system. The results obtained using capillary depletion method show that tiazofurin that passes across the BBB is accumulated mostly in the brain tissue and not in brain capillaries endothelial cells.