title: Pharmacokinetics of intratumoral RK-28, a new hypoxic radiosensitizer.
abstract: RK-28 is one of the new hypoxic cell radiosensitizers being developed in Japan and has been tested clinically. To reduce its toxicity and increase its sensitizing activity, intratumoral injection of RK-28 was performed during intraoperative radiation therapy for pancreatic cancer. This report presents the results of pharmacokinetic studies performed in 10 of the 17 patients who were administrated intravenous or intratumoral RK-28 during intraoperative radiation therapy. No adverse effects were noted following intravenous or intratumoral injection of the drug. Pharmacokinetic studies demonstrated several metabolites of RK-28 in both serum and tumor tissues. After intratumoral injection, the tumor drug concentration ranged from 123 micrograms/g to 9,292 micrograms/g just after intraoperative radiation therapy (30-50 min after injection of the compound), while the serum concentration ranged from 4.1 to 9.8 micrograms/ml. The tumor drug concentration was 23.3 micrograms/g at 45 min after intravenous injection of RK-28. Thus, intratumoral injection of RK-28 was superior to intravenous administration in this pharmacokinetic study. The combination of intraoperative radiation therapy and intratumoral injection of RK-28 appears to be a feasible treatment method.
authors.affiliation: Department of Radiology, Kyoto University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sasai
authors.forename: Y
authors.initials: Y
authors.lastname: Shibamoto
authors.forename: T
authors.initials: T
authors.lastname: Manabe
authors.forename: N
authors.initials: N
authors.lastname: Baba
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: M
authors.initials: M
authors.lastname: Abe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*
chemical_list: D011838:Radiation-Sensitizing Agents; C047778:1-(4'-hydroxy-2'-butenoxy)methyl-2-nitroimidazole; D008920:Misonidazole