STUDY ON TRANSCATHETER EMBOLIZATION FOR RENAL CARCINOMA

3rd Report—Bioavailability of Anti-cancer Agent (Adriamycin) Administered During Transcatheter Embolization

Abstract

Adriamycin was given to rats for the purpose of establishing an effective dosing method of chemotherapeutic agents for malignant renal carcinoma. The rats were divided into three groups, 1) intravenous injection group given a single dose of 5mg/kg into the caudal vein, 2) arterial injection group given a single dose of 1mg/kg into the renal artery and 3) embolization group undergoing transcatheter embolization of the renal artery with a gelatine sponge containing 1/mg/kg. Pharmacokinetics of adriamycin in these groups were investigated and the following results were obtained.
1. The serum concentration of adriamycin 1 hour after dosing was 0.74±0.05μg/ml (mean±standard error) in the intravenous injection group, 0.22±0.04μg/ml in the arterial injection group and 0.21±0.06μg/ml in the embolization group. Serum concentration thereafter was maintained at low levels in the descending order of intravenous injection, arterial injection and embolization. The drug became undetectable 6 hours after dosing in the arterial injection group, and 48 hours after dosing in both intravenous injection and embolization groups.
The half life of adriamycin in the blood was 6.5 hours by intravenous injection, 1.4hours by embolization and 1.2 hours by arterial injection.
2. The peak concentration of adriamycin in the kidneys was 45.39±8.90μg/g 2 hours after dosing in the intravenous injection group, 48.57±7.65μgg 1 hour after dosing in the arterial injection group and 170.45±37.39/μg 1 hour after dosing in the embolization group. The renal concentration of the drug thereafter changed similarly in both intravenous injection and arterial injection groups, wheras it was approximately 3 to 6 times higher in the embolization group than in the two other groups.
The half life of adriamycin in the kikneys was 63 hours by intravenous injection, 58 hours by embolization and 46 hours by arterial injection.
3. The concentrations of adriamycin in organs other than the kidneys were as follows:
a. The peak concentration in the liver was 47.32±4.88μg/g 2 hours after dosing in the intravenous injection group, 9.23±1.31μg/g 2 hours after dosing in the arterial injection group and 13.76±0.53μg/g 1 hour after dosing in the embolization group. The drug concentrations thereafter changed similarly in the arterial injection and embolization groups, and were approximately 1/3 to 1/6 of those of the intravenous injection group.
b. The peak concentration of adriamycin in the prostate was 6.07±0.22μg/g 2 hours after dosing in the intravenous injection group, 1.47±0.60μg/g 3 hours after dosing in the arterial injection group and 0.97±0.17μg/g 2 hours after dosing in the embolization group. The drug concentrations therafter changed similarly in the arterial injection and embolization groups and was approximately 1/5 to 1/17 of those of the intravenous injection group.
c. The peak concentration of adriamycin in the bladder was 7.19±1.03μg/g 2 hours after dosing in the intravenous injection group, 3.46±0.74μg/g 1 hour after dosing in the arterial injection group and 1.46±0.15μg/g 3 hours after dosing in the embolization group. The drug concentrations thereafter changed similarly in the arterial injection and embolization groups and were approximately 1/2 to 1/8 of those of the intravenous injection group.
d. The peak concentration of adriamycin in the lymph nodes was 19.23μg/g 2 hours after dosing in the intravenous injection groups, 7.71μg/g 1 hour after dosing in the arterial injection group and 5.65μg/g 1 hour after dosing in the embolization group. The drug concentrations thereafter changed similarly in the arterial injection and embolization groups and were approximately 1/4 to 1/20 of those of the intravenous injection group.
e. The half life of adriamycin in the intravenous injectio