PMID- 24800921
OWN - NLM
STAT- MEDLINE
DCOM- 20140925
LR  - 20181202
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 52
IP  - 8
DP  - 2014 Aug
TI  - Lack of a clinically relevant effect of sugammadex on anti-Xa activity or 
      activated partial thromboplastin time following pretreatment with either 
      unfractionated or low-molecular-weight heparin in healthy subjects.
PG  - 631-41
LID - 10.5414/CP202091 [doi]
AB  - OBJECTIVE: To investigate the potential effect of sugammadex on anti-Xa 
      anticoagulantactivity of enoxaparin and the activated partial thromboplastin time 
      (APTT) of unfractionated heparin (UFH). METHODS: This two-part, randomized, 
      double-blind, placebocontrolled, four-period cross-over study was performed in 
      healthy males (18 - 45 years). In each period, subjects received 40 mg enoxaparin 
      (in part 1), 5,000 units UFH (in part 2), or placebo followed by 4 or 16 mg/kg 
      sugammadex, or placebo. Treatments were separated by >/= 4 days. Primary endpoints 
      were anti-Xa activity and APTT both time-averaged from 3 to 30 minutes post-dose. 
      Geometric mean ratios (GMRs) and their two-sided 90% confidence limits were 
      calculated for anticoagulant plus sugammadex (4 or 16 mg/kg) vs. anticoagulant 
      plus placebo. The pre-specified threshold for a potential effect of clinical 
      relevance was a 90% upper confidence limit (UCL) > 1.50. RESULTS: In part 1 (n = 
      13), the 90% UCLs were 1.07 and 1.08 for GMRs of anti-Xa activity after dosing 
      with 4 and 16 mg/kg sugammadex, respectively. In part 2 (n = 43), the 90% UCLs 
      for GMRs of APTT were 1.06 and 1.15. Neither sugammadex dose produced a treatment 
      effect that met the pre-specified criterion for potential clinical relevance. 
      Treatments were generally well tolerated. CONCLUSIONS: In healthy subjects, 
      treatment with 4 mg/kg and 16 mg/kg sugammadex did not change either anti-Xa 
      activity or APTT to a clinically meaningful extent following pretreatments with 
      enoxaparin or UFH.
FAU - De Kam, Pieter-Jan
AU  - De Kam PJ
FAU - Kruithof, Annelieke C
AU  - Kruithof AC
FAU - van Lierop, Marie-Jose
AU  - van Lierop MJ
FAU - Moerland, Matthijs
AU  - Moerland M
FAU - Dennie, Justin
AU  - Dennie J
FAU - Troyer, Matthew D
AU  - Troyer MD
FAU - Langdon, Ronald B
AU  - Langdon RB
FAU - Gutstein, David E
AU  - Gutstein DE
FAU - Burggraaf, Jacobus
AU  - Burggraaf J
FAU - El Galta, Rachid
AU  - El Galta R
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (gamma-Cyclodextrins)
RN  - 361LPM2T56 (Sugammadex)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anticoagulants/*pharmacology
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Interactions
MH  - Enoxaparin/*pharmacology
MH  - *Factor Xa Inhibitors
MH  - Heparin/pharmacology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Partial Thromboplastin Time
MH  - Sugammadex
MH  - Young Adult
MH  - gamma-Cyclodextrins/administration & dosage/*pharmacology
EDAT- 2014/05/08 06:00
MHDA- 2014/09/26 06:00
CRDT- 2014/05/08 06:00
PHST- 2014/07/31 00:00 [accepted]
PHST- 2014/05/08 06:00 [entrez]
PHST- 2014/05/08 06:00 [pubmed]
PHST- 2014/09/26 06:00 [medline]
AID - 11484 [pii]
AID - 10.5414/CP202091 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2014 Aug;52(8):631-41. doi: 10.5414/CP202091.