PGH2 receptor blocker and thromboxane synthetase inhibitor, in healthy volunteers

76

POSTER PRESENTATIONS P-7: Thrombolytic Strategies

209 PHARMACODYNAMICS AND TOLERABILITY A NOVEL COMBINED OF DT-TX 30 SE, RECEPTOR BLOCKER AND TXAiPGH2 THROMBOXANE SYNTHETASE INHIBITOR, IN HEALTHY VOLUNTEERS Naries H1, Miiller TH2, Weisenberger Hz, Kirchner M2, Deichsei G1 ‘BOEHRINGER INGELHEIM DEUTSCHLAND GMBH AND 2DR. KARL THOMAE GMBH, D-88397 BIBERACH Escalating single oral doses of 25, 50, 100, 200 and 400 mg DT-TX 30 SE as a drinking solution were administered to healthy volunteers. At each dose level 6 volunteers received active treatment and 2 placebo (double blind randomized). Primary endpoint was the inhibition of platelet aggregation determined by collageninduced whole blodd aggregometry and collagen-induced plateret aggregation in platelet rich plasma. Thromboxane

membrane structure, glycoproteins and function after thmmbolytic treatment M.Kicifiska; *J.G6rski IV Clinic of Internal Diseases Medical Academy, Gdafisk, *Institute of Maritime and Tropical Medicine, Gdynia, POLAND

210 Platelet

The aim of this study was to elucidate the mechanism of platelet disfunction in 19 pts with A'41 treated with streptokinase (SK). Before and 1 hour after SK infusion, the following determinations were performed: platelet aggregation with AOP, collagen (C) and ristocetine (R),plasma hetathromboglobulin (PTG) concentration,platelet (GP) Ib and IIb/IIIa (with membrane glycoproteins monoclonal antibodies) and platelet membrane structure using a spin marker (MSL) that binds to the -Sli and -NH2 groups of membrane proteins and analysing the hs+l/hw+l ratio of the ESR spectrum (indices of membrane fluidity).

211 EFFECTS OF CAPTOPRIL,METOPROLOL AND CAPTOPRILDURING THROMBOLYSIS.PRELIMINARY Di Pasquale P,Paterna S,Bucca G,Pipitone F,Caracausi R,Rinciari G.F.Ingrassia Hospital.Department

RESULTS. V,Corrao S,Licata G. Internal Medicine,

University

of Palermo,ItaIy.

The study

was aimed to verify,during

in patients on(AMI),the

with anterior acute safety and effects

thrombolysis(T)

myocardiai infarctiof beta-blockers(BB)

or captopril(C) and their association(C+BB).166 pts hospitalised within 4 hs from the onset of symptoms (1st episode),eligible for T,Killip’s class l-2,were randomised (single blind) into 4 groups.Group A(42 pts) received 6.25 mg C orally 15 min before T and BB 5 mgX3 iv within 1 h.Group B(42 pts:6.25 mg C.Group C (37 pts) BB only.Group D (45 pts) T onIy.After 3 days C and D also received C.We checked:ventricular arrhythmias(VA).early(first 2 hs) and late (Lawn’s class 2)&K peak,Normalization time of CK (NTE) and Mortality at. follow-up (30~5

receptor antagonism, thromboxane synthetase inhibition and 6-keto-PGFla in plasma were also determined. In addition to general health, safety was assessed by measuring bleeding time, hematuria, fecal blood loss and routine laboratory parameters including coagulation assays. Plasma concentrations of DT-TX 30 SE were measured. Measurement of whole blood aggregation showed a dose-dependent increase of inhibition between 55% (25 mg) and 90% (400 mg). Platelet aggregation in platelet rich plasma showed a reduction in collagen sensitivity of about 4-fold in response to 25 mg and ?Ofold in response to 400 mg. A dose-dependent thromboxane receptor antagonism and inhibition of thromboxane synthetase as well as an increase of 6-ketoPGFla were observed. DT-TX 30 SE was well tolerated.

RESULTS: (expressed as % of decrease, crease, 7,after SK infusion) aggregation * AflP 4 47,3 c R

t 10,5 4

992

GP I h * 4 20,6

hs+l/hw+l + 4

GP IIb/IIIa 4 1133

A, or in-

22,0 TG

* t

19,4

* 0<0,05 COIICLUSIflHS:

in pts with AM1 treated l.Platelet disaggregation with SK may be attributed to the decrease in platelet membrane GP Ib and IIb/IIIa and increase of membrane fluidity. Z.Increase in plasma PTG concentration is an evidence of simultaneous platelet activation. 3.Platelet disaggregation after SK may he the reason for bleedings in AM1 pts, whereas platelet activation may contribute to coronary rethrombosis.

months);Resul!x:VA early:group A 5 cases,B 5,C 15,D 16.Late VA:A 5,B 8,C 10,D 16.CK peak:A 1875.8 1566.C 2274.D 2103 u/I.NTE:A 57,B 58,C 72,D 69 hs.Mortality:A 2,B 3,C 6,D 8 pt.s.Our data suggest. a greater beneficial pffects of captopril and addition of BB does not add further advantages compared with C pretreatment