Clinico-Pharmacological Studies of Factor VIII Response After DDAVP

This study evaluates how FVIII coagulant activity (VIIIC) and FVIII-related antigen(VIII RAG) behave in response to intravenous (i.v.) and intranasal (i.n.) DDAVP in healthy volunteers 6 subjects received 4 i v. doses of DDAVP (0.1-0.4 µg/Kg)and placebo in random order Changes of VIIIC and VIII RAG were measured from baseline after 30 and 90 min VIII:C increased with dose and reached a plateau at 0.3 µg/Kg. VIII RAG showed a smaller increase and attained a plateau at 0. 2 µg/Kg. 5 other subjects were treated under identical conditions with i. n. DDAVP, There was a consistent rise of VIIIC with all the tested doses (1-4 µg/Kg), but no dose-response relationship. The disappearance ot VIIIC and VIII RAG was measured in 6 different subjects receiving a single i.v. dose of DDAVP (0.4 µg/Kg), VIIIC showed a mean biologic half-life of 292 min (range: 150-375); VIII RAG half-life was 615 min (450-840). A final group of 6 subjects were given daily i.v. doses of DDAVP (0.4 µg/Kg) to asses consistency in response After 3 doses the response began to decrease. However, even the 5th dose gave an increase over baseline of VIIIC and VIII RAG. Thus, i. v. DDAVP produces its maximal response at 0.3 μg/Kg Intranasal DDAVP, although less predictable, is capable of elevating VIIIC and may be adoptable for providing high VIIIC levels in blood donors. After i v. DDAVP. the disappearance time of VIIIC is shorter than that of VIII:C given with F. VIII concentrates and a decreased response tends to develop after repeated doses.