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• W2313746536 abstract "SUMMARY 33 The brain penetration of a novel MDR-reversing cyclosporin, SDZ PSC 833, was studied by measuring brain and blood concentrations after intravenous administration either as a bolus or as a constant-rate infusion. At lower blood concentrations ofSDZ PSC 833, the brain penetration defined as the brain-to-blood concentration ratio (Kp), was very low in spite of the high lipophilicity of this compound. At higher blood concentrations, however, the brain penetration ofSDZ PSC 833 was markedly increased. Since the blood pharmacokinetic ofSDZ PSC 833 was found to be linear in the dosage range studied, these results demonstrated a non-linear brain penetration of SDZ PSC 833. The brain passage of cyclosporin A was also found to obey a non-linear kinetic. However the potency ofSDZ PSC 833 to inhibit the efflux mechanism at the blood-brain barrier (BBB) was higher than that of the cyclosporin A since I 0 times higher doses of cyclosporin A were required to obtain the same KP values as SDZ PSC 833. Moreover, the coadministration ofSDZ PSC 833 increased the brain penetration of cyclosporin A whereas the latter did not modify that of SDZ PSC 833. The increase in Kr values for SDZ PSC 833 observed at high blood leYels ofSDZ PSC 833 are consistent with the hypothesis that SDZ PSC 833 governs its own brain passage possibly by inhibition of the P-glycoprotein pump present in the brain microcapillary endothelial cells." @default.
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• W2313746536 date "1996-01-01" @default.
• W2313746536 modified "2023-09-27" @default.
• W2313746536 title "BRAIN PENETRATION OF SDZ PSC 833 IN RATS A Comparison with Cyclosporin A" @default.
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