Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077). II. Hydrolysis by tissue homogenates and drug uptake by tumor cells in vitro.

Abstract

1-(2-Chloroethyl)-3-isobutyl-3-(beta-maltosyl)-1-nitrosourea (TA-077) was hydrolyzed to its glucosyl metabolite TA-G by homogenates of guinea pig organs, rabbit VX-2 carcinoma and rat Yoshida sarcoma. The rate of TA-G formation by the kidney was the highest among the tissues examined and that by the diluted blood was undetectably low, reflecting their maltase activities. TA-077 was also hydrolyzed by suspensions of Yoshida sarcoma, AH130 hepatoma, L1210 leukemia, P388 leukemia and DBLA-10/C leukemia cells. The rate of TA-G formation was increased 10 fold by homogenizing the tumor cells. TA-G was taken up by the tumor cells much more efficiently than TA-077, explaining the higher sensitivities of the cultured tumor cells to TA-G than to TA-077. However, neither the maltase activity nor the membrane permeability to the drugs was a factor influential enough to explain the differences in drug sensitivity among the tumor cell lines.

• Authors: K Hayashida, K Oda, Y Akaike, Y Arai, S Takeyama
• Journal: Journal of pharmacobio-dynamics (J Pharmacobiodyn) Vol. 10 Issue 10 Pg. 515-22 (Oct 1987) ISSN: 0386-846X [Print] Japan
• PMID: 3326928 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Glycoside Hydrolase Inhibitors
• Nitrosourea Compounds
• TA 077
• alpha-Glucosidases

Topics

• Animals
• Antineoplastic Agents (blood, pharmacokinetics)
• Female
• Glycoside Hydrolase Inhibitors
• Guinea Pigs
• Hydrolysis
• In Vitro Techniques
• Male
• Nitrosourea Compounds (blood, pharmacokinetics)
• Rabbits
• Tumor Cells, Cultured (metabolism)
• alpha-Glucosidases (metabolism)