PMID- 21549797
OWN - NLM
STAT- MEDLINE
DCOM- 20111215
LR  - 20110711
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 60
IP  - 3
DP  - 2011 Aug
TI  - A dose-response study in animals to evaluate the anticoagulant effect of the 
      stage 2 unfractionated heparin USP monograph change.
PG  - 318-22
LID - 10.1016/j.yrtph.2011.04.008 [doi]
AB  - The United States Pharmacopeia (USP) monograph for unfractionated heparin (UFH) 
      was revised in October 2009. This revision was anticipated, based upon in vitro 
      tests, to reduce UFH potency by approximately 10%. To study the potential in vivo 
      consequences of the monograph change, we evaluated activated partial 
      thromboplastin time (aPTT) and activated clotting time (ACT) responses in 
      animals. Female mini-pigs and monkeys (n=8/species) were administered 
      intravenously 60, 54, 48, or 42 U/kg and 50, 45, 40, or 35 U/kg "old" (pre-USP 
      revision) UFH, respectively, in a Williams 4x4 crossover design. Blood samples 
      for aPTT and ACT were collected at 15 min after dosing. The same study design was 
      then repeated using "new" (post-USP revision) UFH. Mean "new" UFH aPTT and ACT 
      values were generally lower than those for "old" UFH although individual animal 
      responses varied considerably. The aPTT and ACT response was generally 
      dose-proportional for both "old" and "new" UFH. These studies indicate that the 
      USP monograph alteration for UFH may result in a modest reduction in the 
      anticoagulant response across a population, but the variability in animal 
      responses underscores the importance of individualization of clinical UFH dosing 
      and the importance of anticoagulant test monitoring.
CI  - Published by Elsevier Inc.
FAU - Honchel, R
AU  - Honchel R
AD  - Division of Medical Imaging Products, Office of New Drugs, Center for Drug 
      Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, 
      USA. ronald.honchel@fda.hhs.gov
FAU - Carraway, J
AU  - Carraway J
FAU - Gopee, N
AU  - Gopee N
FAU - Callicott, R
AU  - Callicott R
FAU - Chen, J
AU  - Chen J
FAU - Patton, R
AU  - Patton R
FAU - Xu, Q
AU  - Xu Q
FAU - Zalkkar, J
AU  - Zalkkar J
FAU - Laniyonu, A
AU  - Laniyonu A
FAU - Krefting, I
AU  - Krefting I
FAU - Cato, M
AU  - Cato M
FAU - Robie-Suh, K
AU  - Robie-Suh K
FAU - Rieves, R
AU  - Rieves R
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110429
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology/toxicity
MH  - Blood Coagulation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Monitoring/methods
MH  - Female
MH  - Haplorhini
MH  - Heparin/*pharmacology/toxicity
MH  - Partial Thromboplastin Time/methods
MH  - Swine
MH  - United States
MH  - Whole Blood Coagulation Time/methods
EDAT- 2011/05/10 06:00
MHDA- 2011/12/16 06:00
CRDT- 2011/05/10 06:00
PHST- 2011/02/03 00:00 [received]
PHST- 2011/04/21 00:00 [revised]
PHST- 2011/04/23 00:00 [accepted]
PHST- 2011/05/10 06:00 [entrez]
PHST- 2011/05/10 06:00 [pubmed]
PHST- 2011/12/16 06:00 [medline]
AID - S0273-2300(11)00076-6 [pii]
AID - 10.1016/j.yrtph.2011.04.008 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2011 Aug;60(3):318-22. doi: 10.1016/j.yrtph.2011.04.008. 
      Epub 2011 Apr 29.