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
T YajimaT Kawaguchi

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 almost complete, 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 were 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 the CSF at a concentration higher than that of D4T, although transport of the intact prodrug to the CSF was not observed following i.v. administration. These results suggest that direct transport of the drugs from the nasal cavity to the CSF significantly contributes to the higher concentrations in CSF of D4T and/or its ester prodrugs, and...Continue Reading

Citations

Feb 12, 2013·Bioanalysis·Robin DiFrancescoGene D Morse
May 17, 2005·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Joke P M in 't VeenFrans W H M Merkus
Apr 8, 2010·Pharmaceutical Research·Yin Cheong Wong, Zhong Zuo
Dec 1, 2001·Expert Opinion on Biological Therapy·G S TirucheraiA K Mitra
Aug 23, 2008·Drug Delivery·T GovenderI Mackraj
Dec 12, 2003·Journal of Drug Targeting·Mascha P Van den BergFrans W H M Merkus
Nov 17, 2004·Reviews in Medical Virology·Nathalie Strazielle, Jean-François Ghersi-Egea
May 3, 2007·Drugs in R&D·Frans W H M Merkus, Mascha P van den Berg
Jun 6, 2000·Advanced Drug Delivery Reviews·X Li, W K Chan

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