Radiosensitization by 2-nitroimidazole nucleoside analog RP-170: radiosensitizing effects under both intravenous and oral administration.

Abstract

The radiosensitizing activity, pharmacokinetics and toxicity of RP-170, 2-nitroimidazole nucleoside analog, were investigated and compared with those of etanidazole (SR-2508). An intravenous administration (i.v.) of 100 mg/kg of RP-170 or the same dose of etanidazole showed an equal sensitizer enhancement ratio (SER) of about 1.4 to solid EMT6 tumor under in vivo-in vitro assay and a virtually equal SER of 1.4-1.5 to solid SCC VII tumor under tumor growth delay assay. As predicted from the low partition coefficient, lower drug levels in neural tissue and more rapid serum elimination of RP-170 and etanidazole produced lower acute toxicity than lipophilic sensitizers (e.g., misonidazole). The major advantage of RP-170 over etanidazole is that it has a second route of administration. In contrast to etanidazole, in which the administration route is limited to intravenous injection, with RP-170 oral administration also exhibited effective distribution to tumors, sensitizing radiation activity to solid EMT6 and SCC VII tumors. Moreover, LD50 in mice of RP-170 (4.3 g/kg on i.v.) was increased to 5.2 g/kg by oral administration. This availability of two routes of administration indicates RP-170 as a promising hypoxic cell radiosensitizer for clinical use.

• Authors: C Murayama, A Suzuki, C Sato, Y Tanabe, Y Miyata, T Shoji, T Suzuki, M Sakaguchi, T Mori
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 22 Issue 3 Pg. 557-60 ( 1992) ISSN: 0360-3016 [Print] United States
• PMID: 1531214 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitroimidazoles
• Nucleosides
• Radiation-Sensitizing Agents
• RP 170
• Etanidazole

Topics

• Administration, Oral
• Animals
• Combined Modality Therapy
• Etanidazole
• Female
• Injections, Intravenous
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy, radiotherapy)
• Nitroimidazoles (administration & dosage, pharmacokinetics, toxicity)
• Nucleosides (administration & dosage, pharmacokinetics, toxicity)
• Radiation-Sensitizing Agents (administration & dosage, pharmacokinetics, toxicity)
• Rats
• Rats, Inbred Strains