COMPARISON OF THE IV AND IP ROUTES OF ADMINISTRATION OF CISPLATIN IN DOGS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 65  (11-1) , 1055-1062
Abstract
Cisplatin at a dose of 3 mg/kg was administered to dogs either i.v. or i.p. Cisplatin concentrations in serum, urine and tissues were measured with a radioisotope tracer method employing 195mPt cisplatin. Systemic toxicity was monitored by serial BUN [blood urea N], creatinine and wbc [white blood cell] and platelet counts. The mode of administration did not affect systemic toxicity since the changes in renal and bone marrow functions were identical in the 2 groups. Serum cisplatin levels following i.v. administration peaked at 13.5 .mu.g/ml at 5 min and were biphasic with rapid initial decline and a prolonged elimination phase. Levels following i.p. administration increased rapidly to 1.5 .mu.g/ml at 4 h and then decreased with the i.v. levels. The amount of drug recovered in the urine was similar regardless of method of administration, with .apprx. 50% of the injected dose excreted by Day 4. The drug levels within the tissues on Days 4 and 8 were similar, with the exception of the tissues lining the peritoneal cavity. On Day 4 the tissues lining the peritoneal cavity had 2.5-8 times higher levels of drug after i.p. administration; this difference was statistically significant (P < 0.01). Local toxic effects encountered with i.p. administration consisted of bloody ascites on Day 4 (4 of 9 dogs) and filmy adhesions on Day 8 (1 of 4 dogs). I.p. cisplatin chemotherapy evidently may increase the therapeutic index for small tumors which are confined to the peritoneal cavity.