The influence of the route of administration of nitrogen mustard and melphalan upon their anti-tumour activity in the rat

✍ Scribed by L. M. Cobb

• Publisher: John Wiley and Sons
• Year: 1966
• Tongue: French
• Weight: 603 KB
• Volume: 1
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910010404

✦ Synopsis

The influence of routes of administration upon the therapeutic activity and lethal effect of nitrogen mustard ( H N 2 ) and Melphalan is described. The intra-arterial, intravenous, intraperitoneal and intraportal routes were used and logarithmic doseresponse curves constructed for cure-rate of the established Walker rat carcinosarcoma 256 and for the LDs0. From these results therapeutic indices were calculated. These indices (LD,,/ED,) for HN2 were 50, 30, 7.5 and 7.5 respectively. Intraperitonealand intraportal injection of H N 2 greatly reduced the anti-tumour activity by comparison with intravenous and intra-arterial injection. It appears that the loss of activity of intraportally injected H N 2 is effected, to a large extent, on the initial passage through the liver. The reduction in activity that occurs with intraperitoneal injections is also thought to be partly due to this effect by the liver. Evidence is presented that lethal intraperitoneal doses of H N 2 produce their effect upon the intestinal tract largely without passing into the general blood circulation. It is suggested that the drug passes directly through the intestinal wall to bring about the destruction of the lining epithelium. The LDao for H N 2 was similar for the four routes of administration. The possible reasons f o r this are discussed. The route of administration did not influence the therapeutic index for Melpha-Ian.