PMID- 11560562
OWN - NLM
STAT- MEDLINE
DCOM- 20011011
LR  - 20190513
IS  - 0306-5251 (Print)
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 52
IP  - 3
DP  - 2001 Sep
TI  - Pharmacodynamic characterization of the interaction between abciximab or 
      tirofiban with unfractionated or a low molecular weight heparin in healthy 
      subjects.
PG  - 297-305
AB  - AIMS: The objective of our study was to define the interaction between either 
      unfractionated heparin (UFH) or a low molecular weight heparin, reviparin (REV), 
      and the pharmacodynamic profile of the GPIIb/IIIa-antagonists abciximab (ABC) or 
      tirofiban (T). METHODS: Two studies each containing 18 healthy subjects were 
      performed, and all were pretreated with aspirin (ASA) for 3 days. Volunteers then 
      received UFH (5000 IU bolus/infusion 7 IU kg(-1) h(-1) for 7 h, n = 6), REV 
      (4200-anti-Xa-IU s.c., n = 6) or placebo (n = 6). One hour later, ABC (study I) 
      or T (study II) were given by i.v. infusion for 6 h. The pharmacodynamic effects 
      measured were bleeding time (BT), fibrinogen-binding at the GPIIb/IIIa-receptor 
      (FIB), expression of the platelet secretion marker CD62, and ADP (20 microM)- and 
      collagen (5 microg ml(-1))-induced platelet aggregation. RESULTS: After treatment 
      with both GPIIb/IIIa-antagonists, prolongation of BT occurred to a similar 
      magnitude (approximately 25-30 min) and was not affected by UFH or 
      REV-comedication. ABC or T with ASA alone resulted in nearly the same magnitude 
      of reduction in FIB and platelet aggregation. After coadministration with UFH, 
      FIB was significantly higher (thus less inhibited) than after after T + ASA alone 
      (19 +/- 16% vs 55 +/- 36%) or ABC + ASA alone (8 +/- 9% vs 32 +/- 11%). This 
      attenuation of FIB was not seen with REV. Inhibition of ADP-and collagen-induced 
      aggregation tended to be attenuated by treatment with UFH (e.g. ADP-induced 
      aggregation at 0.25 h after ABC + ASA alone =13 +/- 4%; after coadministration 
      with UFH = 40 +/- 26%). No such changes were noted with REV. Minor reductions in 
      CD62-expression were seen in subjects given ABC or T alone, but expression was 
      not affected by UFH or REV. CONCLUSIONS: Co-medication with UFH attenuated 
      platelet inhibition during treatment with GPIIb/IIIa-antagonists, but these 
      effects were not seen with the low molecular weight heparin reviparin. The 
      results show that administration of reviparin together with abciximab or 
      tirofiban did not adversely affect the pharmacodynamic profile of these 
      GPIIb/IIIa-antagonists.
FAU - Klinkhardt, U
AU  - Klinkhardt U
AD  - Institute of Clinical Pharmacology, University Hospital, Frankfurt a.M., Germany.
FAU - Graff, J
AU  - Graff J
FAU - Westrup, D
AU  - Westrup D
FAU - Kirchmaier, C M
AU  - Kirchmaier CM
FAU - Esslinger, H U
AU  - Esslinger HU
FAU - Breddin, H K
AU  - Breddin HK
FAU - Harder, S
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 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Platelet Glycoprotein GPIIb-IIIa Complex)
RN  - 0 (Selectins)
RN  - 42HK56048U (Tyrosine)
RN  - 5R0L1D739E (reviparin)
RN  - 9001-32-5 (Fibrinogen)
RN  - 9005-49-6 (Heparin)
RN  - GGX234SI5H (Tirofiban)
RN  - X85G7936GV (Abciximab)
SB  - IM
MH  - Abciximab
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal/pharmacology
MH  - Anticoagulants/*pharmacology
MH  - Binding, Competitive/drug effects
MH  - Bleeding Time
MH  - Blood Platelets/drug effects/metabolism
MH  - Drug Interactions
MH  - Factor Xa Inhibitors
MH  - Fibrinogen/metabolism
MH  - Flow Cytometry
MH  - Heparin/pharmacology
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Humans
MH  - Immunoglobulin Fab Fragments/pharmacology
MH  - Male
MH  - Partial Thromboplastin Time
MH  - Platelet Aggregation/drug effects
MH  - Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors/metabolism
MH  - Selectins/drug effects/metabolism
MH  - Tirofiban
MH  - Treatment Outcome
MH  - Tyrosine/analogs & derivatives/pharmacology
PMC - PMC2014552
EDAT- 2001/09/19 10:00
MHDA- 2001/10/12 10:01
PMCR- 2002/09/01
CRDT- 2001/09/19 10:00
PHST- 2001/09/19 10:00 [pubmed]
PHST- 2001/10/12 10:01 [medline]
PHST- 2001/09/19 10:00 [entrez]
PHST- 2002/09/01 00:00 [pmc-release]
AID - bcp1446 [pii]
AID - 10.1046/j.0306-5251.2001.01446.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2001 Sep;52(3):297-305. doi: 
      10.1046/j.0306-5251.2001.01446.x.