Pharmacokinetics of 4-[4"-(2",2",6",6"-tetramethyl-1"-piperidinyloxy) amino]-4'-demethylepipodophyllotoxin in mice bearing sarcoma 180

Abstract

Aim: To study the pharmacokinetics of 4-[4"-(2",2",6",6"-tetramethyl- 1"-piperindyloxy) amino]-4'-demethylepipodophyllotoxin (GP-7) in mice bearing sarcoma 180.

Method: Using HPLC with a uv detector at 285 nm.

Results: The plasma concentration-time course of GP-7 in mice was best fitted to a 2-compartment open modle after iv 20, 60 mg.kg-1. At both doses the plasma T1/2 beta was around 40 min. The highest concentration was found in liver and lung. The level of GP-7 was higher in tumor than in kidney, spleen, and bone marrow after ip 20 mg.kg-1 for 10 d. Urinary excretion of GP-7 as unchanged drug accounted for about 20% of the administered doses 72 h after injection.

Conclusion: GP-7 disappeared more slowly from the plasma of mice bearing sarcoma 180, distributed extensively over the tissues and was partially excreted from urine. The concentrition of GP-7 in tumor was higher.