Pharmacokinetic characteristics of L-valyl-ara-C and its implication on the oral delivery of ara-C

Eun Pa Cheon, Hyo Kyung Han

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Pages (from-to)268-272
Number of pages5
JournalActa Pharmacologica Sinica
Volume28
Issue number2
DOIs
StatePublished - Feb 2007

Keywords

  • Ara-C
  • L-valyl-ara-C
  • Pharmaco-kinetics
  • Prodrug
  • Rats

Fingerprint

Dive into the research topics of 'Pharmacokinetic characteristics of L-valyl-ara-C and its implication on the oral delivery of ara-C'. Together they form a unique fingerprint.

Cite this