DEVELOPMENT OF AN ELISA FOR THE MEASUREMENT OF DSPA(ALPHA-1) (DESMODUS-ROTUNDUS SALIVARY PLASMINOGEN-ACTIVATOR) IN PLASMA AND ITS APPLICATION TO INVESTIGATE PHARMACOKINETICS IN MONKEYS

DSPA(alpha 1) is a novel plasminogen activator with high fibrin specif icity. A sandwich ELISA-system with affinity purified and peroxidase l abelled DSPA(alpha 1) antibodies raised in rabbits was developed and e xhibited a limit of quantification of 3 ng/ml in undiluted spiked plas ma. Accuracy was 98-108% and precision accounted for 3-9.5%. No cross- reactivity with human t-PA or endogenous matrix constituents interferi ng with assay results was observed. After i.v. administration DSPA(alp ha 1) at 1 and 3 mg/kg in cynomolgus monkeys antigen levels in plasma were dose-dependent in both gender and exhibited a triphasic dispositi on profile with half-lives of 0,04-0,26 h, 0.6-3 h and 4-8.5 h, The me an residence time of DSPA(alpha 1) ranged from 3 to 9 h and total clea rance was approximately 2 mg/min/kg independent of sex and dose. These data obtained in monkeys showed a long systemic circulation of the an tigen, linear pharmacokinetics and no sex-specific pharmacokinetic dif ferences in the dose range investigated. In conclusion the present ELI SA method is suitable for pharmacokinetic studies of DSPA(alpha 1) in animals and man. First investigations in monkeys demonstrated the inte resting pharmacokinetic profile of the compound which might be adminis tered by i.v. bolus administration for the treatment of acute myocardi al infarction.