The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the sheep

Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin was determined in relation to the recovery of [14C]-mannitol by me...

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Veröffentlicht in:Methods and findings in experimental and clinical pharmacology 2000-04, Vol.22 (3), p.149-154
Hauptverfasser: REDZIC, Z. B, SEGAL, M. B, GASIC, J. M, MARKOVIC, I. D, ISAKOVIC, A, RAKIC, L. M
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container_issue 3
container_start_page 149
container_title Methods and findings in experimental and clinical pharmacology
container_volume 22
creator REDZIC, Z. B
SEGAL, M. B
GASIC, J. M
MARKOVIC, I. D
ISAKOVIC, A
RAKIC, L. M
description Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin was determined in relation to the recovery of [14C]-mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 +/- 0.84% and was shown to be both carrier-mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 +/- 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a Km of 7.71 +/- 1.42 microM, a Vmax of 1.30 +/- 0.05 microM/min/g and a negligible constant of a free diffusion (Kd) which suggests that the CP/CSF route may act as an alternative pathway into the brain.
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The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a Km of 7.71 +/- 1.42 microM, a Vmax of 1.30 +/- 0.05 microM/min/g and a negligible constant of a free diffusion (Kd) which suggests that the CP/CSF route may act as an alternative pathway into the brain.</description><identifier>ISSN: 0379-0355</identifier><identifier>PMID: 10893696</identifier><language>eng</language><publisher>Barcelona: Prous</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Agents - pharmacokinetics ; Biological and medical sciences ; Blood-Brain Barrier ; Choroid Plexus - metabolism ; General aspects ; Medical sciences ; Perfusion ; Pharmacology. 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source MEDLINE; Portico (Triggered Content) Journals
subjects Animals
Antineoplastic agents
Antineoplastic Agents - pharmacokinetics
Biological and medical sciences
Blood-Brain Barrier
Choroid Plexus - metabolism
General aspects
Medical sciences
Perfusion
Pharmacology. Drug treatments
Ribavirin - analogs & derivatives
Ribavirin - pharmacokinetics
Sheep
title The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the sheep
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