Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Synthesis and In-vitro Evaluation of N4-Amino Acid Derivatives of Cytarabine for Improving the Oral Delivery of Cytarabine

  • Jin, Ming-Ji (BK21 project team, College of Pharmacy, Chosun University) ;
  • Hong, Joon-Hee (BK21 project team, College of Pharmacy, Chosun University) ;
  • Han, Hyo-Kyung (BK21 project team, College of Pharmacy, Chosun University)
  • Published : 2008.08.20
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Abstract

The present study aimed to investigate the in-vitro characteristics of N4-amino acid derivatives of cytarabine for the oral delivery of cytarabine. After the synthesis of L-Ile-cytarabine, L-Leu-cytarabine and L-Arg-cytarabine, the gastrointestinal stability of each prodrug was examined using artificial gastric juice and intestinal fluids. The cellular uptake characteristics of prodrugs were also examined in Caco-2 cells. While L-Ile-cytarabine and L-Leu-cytarabine appeared to be stable in all the tested biological media during 4-hr incubation, L-Arg-cytarabine was rapidly disappeared within 5 min. Accordingly, the cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine was significantly higher than that of its parent drug, cytarabine in Caco-2 cells but the cellular uptake of L-Arg-cytarabine was similar to that from its parent drug. The cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine appeared to be saturable as drug concentration increased from 0.4 to 4 mM. Collectively, L-Ile-cytarabine and L-Leu-cytarabine could be promising candidates to improve the oral absorption of cytarabine via a saturable transport pathway.

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