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Titolo:
DIRECT TRANSPORT OF 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE (D4T) AND ITS ESTER DERIVATIVES TO THE CEREBROSPINAL-FLUID VIA THE NASAL MUCOUS-MEMBRANE IN RATS
Autore:
YAJIMA T; JUNI K; SANEYOSHI M; HASEGAWA T; KAWAGUCHI T;
Indirizzi:
JOSAI UNIV,FAC PHARMACEUT SCI,1-1 KEYAKIDAI SAKADO SAITAMA 35002 JAPAN JOSAI UNIV,FAC PHARMACEUT SCI SAKADO SAITAMA 35002 JAPAN TEIKYO UNIV SCI & TECHNOL,DEPT BIOL SCI YAMANASHI 40901 JAPAN
Titolo Testata:
Biological & pharmaceutical bulletin
fascicolo: 3, volume: 21, anno: 1998,
pagine: 272 - 277
SICI:
0918-6158(1998)21:3<272:DTO2(A>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
BLOOD-BRAIN-BARRIER; ZIDOVUDINE AZT; PRODRUGS; ABSORPTION; SYSTEM; CAVITY; 3'-AZIDO-3'-DEOXYTHYMIDINE; 2',3'-DIDEOXYINOSINE; PHARMACOKINETICS; INFUSION;
Keywords:
CEREBROSPINAL FLUID (CSF); DIDEOXYNUCLEOSIDE; 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE (D3T); AIDS; TRANSPORT; PRODRUG;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
T. Yajima et al., "DIRECT TRANSPORT OF 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE (D4T) AND ITS ESTER DERIVATIVES TO THE CEREBROSPINAL-FLUID VIA THE NASAL MUCOUS-MEMBRANE IN RATS", Biological & pharmaceutical bulletin, 21(3), 1998, pp. 272-277

Abstract

We investigated the absorption and transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester prodrugs from the nasal cavity in rats. The absorption of D4T and its acetate (C2-D4T) was rapid and almostcomplete. although the hemi-succinate (Suc-D4T) was absorbed rather slowly; the plasma concentrations of the prodrug, Suc-D4T, and regenerated D4T remained unchanged throughout the experimental period (180 min). Concentrations in the cerebrospinal fluid (CSF) following intravenous (i.v.) and intranasal (i.n.) administration mere also measured. After i.n. administration, drug concentrations were higher in the fraction derived from the subarachnoid space located close to the nasal mucosa than those in the fractions located far from the nasal cavity. This difference was not found following the i.v. administration of the drugs. Following nasal administration, the intact Suc-D4T was found in theCSF at a concentration higher than that of D4T, although transport ofthe intact prodrug to the CSF was not observed following i.v. administration. These results suggest that direct transport of the drugs fromthe nasal cavity to the CSF significantly contributes to the higher concentrations in CSF of D4T and/or its ester prodrugs, and indicate the possible value of nasal administration for the treatment of patientswith AIDS dementia.

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Documento generato il 22/01/20 alle ore 09:28:18