INFLUENCE OF ROUTE OF ADMINISTRATION ON [H-3] CAMPTOTHECIN DISTRIBUTION AND TUMOR UPTAKE IN CASE BEARING NUDE-MICE - WHOLE-BODY AUTORADIOGRAGHIC STUDIES

Camptothecin (CPT) inhibits the growth of a wide variety of experiment al tumors. As a part of our exploration of this drug for use as a canc er chemotherapeutic agent, we studied the effect of route of administr ation on the absorption, distribution and tumor uptake of [H-3]-CPT. T he rate of disappearance of [H-3]-CPT-derived radioactivity from blood during the first 48 h was highest following oral than following intra venous (i.v.) administration. Thereafter blood levels were low irrespe ctive of route of administration. Considerable [H-3]-CPT-derived radio activity was detected in urine and feces up to 48 h after dosing Distr ibution studies were conducted using quantitative whole-body autoradio graphy (WBA). These studies revealed that independent of the route of administration, [H-3]-CPT was rapidly excreted in the bile (gallbladde r) followed by elimination into the small and large intestinal tract. Levels of CPT-derived radioactivity in the kidneys were minimal and mo stly localized in the renal pelvis. Hepatic concentrations of CPT were low and were almost equal to those of the tumor. The lungs of animals treated i.v. showed higher uptake of radioactivity than those treated intramuscularly or orally. Tumor/blood ratios were slightly higher fo llowing oral administration than following administration by other rou tes. This study indicates that CPT is primarily eliminated via the bil e. The gastrointestinal tract is the major site of accumulation and ex cretion of CPT.