ANTIGENICITY STUDY OF TRANDOLAPRIL (RU44570)

Antigenicity of trandolapril (RU44570) was evaluated using the following six standpoints: 1. active systemic anaphylaxis (ASA) in guinea pigs; 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum of sensitized guinea pigs; 3. histamine release from lung tissue of sensitized guinea pigs; 4. Schultz-Dale reaction with isolated ileum of sensitized guinea pigs; 5. passive cutaneous anaphylaxis (PCA) in rats with serum of sensitized mice; and 6. delayed type skin reaction by Maximization test in guinea pigs. In the test of immediate type reactions, guinea pigs were sensitized by RU44570 (p.o.), an FCA emulsion of RU44570 (s.c.) or an FCA emulsion of incubate solution of RU44570 and normal guinea pig's serum, and mice were sensitized by a mixture of RU44570 and alum (i.p.). In the test of delayed type reaction, guinea pigs were sensitized by intradermal injection and patch application. 1. ASA in guinea pigs: No anaphylaxis symptoms were observed in any of the sensitized guinea pigs. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than l. 3. Histamine release from lung tissue: No histamine release was observed in any of the isolated lung tissue. 4. Schultz-Dale reaction: No contraction was observed in any of the isolated ileums. 5. PCA in rats: PCA titer of sera from sensitized BALB/c and C3H/He mice was less than 5. 6. Delayed type skin reaction test: No skin reactions were observed in any of the sensitized guinea pigs. From these results, it is concluded that RU44570 has no antigenicity under the conditions of the present study.