@article{APS4209,
author = {Eun-pa Cheon and Hyo-kyung Han},
title = {Pharmacokinetic characteristics of L -valyl-ara-C and its implication on the oral delivery of ara-C},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {2},
year = {2016},
keywords = {},
abstract = {Aim: To evaluate the pharmacokinetic characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C.
Methods: After the synthesis of L-valyl-ara-C, the in vitro stability of L-valyl-ara-C was examined in various biological media. Plasma pharmacokinetic profiles of ara-C and L-valyl-ara-C were also evaluated in rats.
Results: The degradation of L-valyl-ara-C was negligible in fresh plasma and also in the presence of plasmin over a 2 h incubation period. Furthermore, L-valyl-ara-C appeared to be stable in the leukemia cell homogenates, and subsequently, it was far less cytotoxic than the parent, ara-C in AML2 and L1210 cells. The chemical hydrolysis of L-valyl-ara-C was rather accelerated in acidic pH. Following an oral administration of L-valyl-ara-C, the appearance of ara-C was observed in plasma although the systemic exposure of the prodrug was much higher than that of ara-C. The bioavailability of ara-C was about 4% via prodrug administration.
Conclusion: The amide bond of L-valyl-ara-C was stable against the enzymatic hydrolysis, and the utility of L-valyl-ara-C as an oral delivery system of ara-C appeared to be limited by its low metabolic conversion to ara-C in rats.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4209}
}