| Autor: |
Høyem S; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, Blindern N-0315 Oslo, Norway., Bruheim S, Maelandsmo G, Olberg DE, Brudeli B, Asberg A, Klaveness J, Rongved P |
| Jazyk: |
angličtina |
| Zdroj: |
European journal of medicinal chemistry [Eur J Med Chem] 2009 Oct; Vol. 44 (10), pp. 3874-9. Date of Electronic Publication: 2009 Apr 14. |
| DOI: |
10.1016/j.ejmech.2009.04.008 |
| Abstrakt: |
Three half-ester derivatives 10-12 of 5'-O-2',3'-dideoxydidanosine (DDI, 1) have been synthesized. The compounds exhibited excellent correlation between partition coefficients LogP and relative in vitro bovine serum albumin binding. Using high-performance liquid chromatography-mass spectrometry (LC-MS), DDI (1) was quantitatively determined in rat plasma after intravenous injection of the azelaic acid monoester derivative (11) of DDI. The pharmacokinetic data obtained for DDI were consistent with literature. The pharmacokinetic profile of 11 showed no significant difference in AUC(0-360) or curve shape compared to the parent drug DDI (1). The data indicate that the prodrug was converted to DDI within minutes after administration. High relative protein binding in vitro holds a promise for validity of the concept using more stable linker bonds. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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