PMID- 12919181
OWN - NLM
STAT- MEDLINE
DCOM- 20040206
LR  - 20190513
IS  - 0306-5251 (Print)
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 56
IP  - 3
DP  - 2003 Sep
TI  - Pharmacodynamic characterization of the interaction between the glycoprotein 
      IIb/IIIa inhibitor YM337 and unfractionated heparin and aspirin in humans.
PG  - 321-6
AB  - AIMS: To investigate the pharmacodynamic interaction of unfractionated heparin 
      (UFH) and acetylic salicylic acid (ASA) on YM337, a monoclonal humanized antibody 
      of the platelet GPIIb/IIIa receptor. METHODS: In a randomized, placebo-controlled 
      study three treatment groups each with six healthy volunteers received the 
      following medication: group 1, ASA (3 days) + UFH + YM337 (placebo); group 2, ASA 
      (placebo) + UFH (placebo) + YM337; group 3, ASA + UFH + YM337. Assessments were 
      made over 24 h and included bleeding time (BT), ADP (20 microm)- and collagen (5 
      microg ml-1)-induced platelet aggregation and PAC1 and CD62 expression measured 
      by flow cytometry. RESULTS: In group 3 BT was prolonged to 35 [median, 16-45 min 
      (1,3 quartile)] after UFH administration, increasing to 45 [median, 42-45 min 
      (1,3 quartile)] after YM infusion (6 h). BT remained elevated to 26 [median, 
      14-45 min (1,3 quartile)] at 24 h, while groups 1 and 2 returned to normal 
      values. Collagen-induced aggregation was 73% [median, 70-80% (1,3 quartile)] 
      under YM337 alone, 79% [median, 72-80% (1,3 quartile)] under ASA + UFH and 
      reduced only in group 3 to 24% [median, 18-29% (1,3 quartile)]. In both groups 
      receiving active YM337, PAC1 expression showed a reduction to < 20% after 6 h of 
      infusion. CD62 expression was not significantly affected by any treatment. 
      CONCLUSION: UFH and YM337 have strong synergistic effects on BT, while 
      coadministration of ASA strongly augments inhibitory effects of YM337 on 
      collagen-induced platelet aggregation.
FAU - Graff, Jochen
AU  - Graff J
AD  - Institute of Clinical Pharmacology, University Hospital Frankfurt, 
      Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. 
      graff@em.uni-frankfurt.de
FAU - Klinkhardt, Ute
AU  - Klinkhardt U
FAU - Westrup, Dagmar
AU  - Westrup D
FAU - Kirchmaier, Carl M
AU  - Kirchmaier CM
FAU - Breddin, Hans Klaus
AU  - Breddin HK
FAU - Harder, Sebastian
AU  - Harder S
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Anticoagulants)
RN  - 0 (E-Selectin)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - EC 3.1.3.48 (DUSP2 protein, human)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 2)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal/pharmacology
MH  - Anticoagulants/*pharmacology
MH  - Aspirin/*pharmacology
MH  - Bleeding Time
MH  - Drug Interactions
MH  - Dual Specificity Phosphatase 2
MH  - E-Selectin/metabolism
MH  - Female
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Male
MH  - Platelet Aggregation
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors
MH  - Protein Phosphatase 2
MH  - Protein Tyrosine Phosphatases/metabolism
PMC - PMC1884347
EDAT- 2003/08/16 05:00
MHDA- 2004/02/10 05:00
PMCR- 2004/03/01
CRDT- 2003/08/16 05:00
PHST- 2003/08/16 05:00 [pubmed]
PHST- 2004/02/10 05:00 [medline]
PHST- 2003/08/16 05:00 [entrez]
PHST- 2004/03/01 00:00 [pmc-release]
AID - 10.1046/j.0306-5251.2003.01873.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2003 Sep;56(3):321-6. doi: 10.1046/j.0306-5251.2003.01873.x.