PMID- 34816442
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220513
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 62
IP  - 6
DP  - 2022 Jun
TI  - Reassessing the Pediatric Dosing Recommendations for Unfractionated Heparin Using 
      Real-World Data: A Pharmacokinetic-Pharmacodynamic Modeling Approach.
PG  - 733-746
LID - 10.1002/jcph.2007 [doi]
AB  - Optimal pediatric dosing of unfractionated heparin (UFH) is challenging because 
      of the paucity of clinical outcome and pharmacokinetic-pharmacodynamic (PK/PD) 
      studies in pediatrics. This study aimed to: (i) develop a PK/PD model for UFH, 
      quantified by anti-factor Xa assay, and the UFH effect, measured by activated 
      partial thromboplastin time (aPTT); and (ii) use simulations to evaluate 
      pediatric UFH infusions for achieving the anti-factor Xa (0.3-0.7 IU/mL) 
      therapeutic target. Electronic health record data were retrospectively collected 
      from 633 patients aged <19 years admitted to Texas Children's Hospital. The PK/PD 
      model was developed using a 70% (training)/30% (testing) split-sample approach. A 
      1-compartment PK model with linear elimination adequately described the UFH PK. 
      An allometrically scaled body weight on clearance (CL) and volume of distribution 
      (Vd) with an age-dependent maturation function of extracellular water on Vd were 
      the covariates identified. Comparable with literature, the typical values for CL 
      and Vd were 3.28 L/(h.50 kg) and 8.83 L/50 kg, respectively. A linear model 
      adequately described the UFH-aPTT relationship with an estimated slope of 150 
      seconds/(IU/mL). Simulations of the currently recommended starting infusions 
      (28 IU/h/kg for pediatrics <1 year old or 20 IU/h/kg for pediatrics >1 year old) 
      showed that the anti-factor Xa therapeutic target was achieved only in 15.3%, 
      14.6%, 36.9%, and 45.11% of subjects in the age groups of <1 year, 1-6 years, 
      6-12 years, and 12-19 years, respectively. In conclusion, the UFH anti-factor Xa 
      target is not achieved initially, especially in young pediatrics, suggesting the 
      need to optimize UFH dosing to achieve higher therapeutic success.
CI  - (c) 2021, The American College of Clinical Pharmacology.
FAU - Salem, Ahmed M
AU  - Salem AM
AUID- ORCID: 0000-0002-2415-8801
AD  - Center for Translational Medicine, Department of Pharmacy Practice, University of 
      Maryland School of Pharmacy, Baltimore, Maryland, USA.
FAU - Niu, Tao
AU  - Niu T
AD  - Modeling & Simulations, Vertex Pharmaceuticals, Boston, Massachusetts, USA.
FAU - Li, Chao
AU  - Li C
AD  - Fosun Pharma, Princeton, New Jersey, USA.
FAU - Moffett, Brady S
AU  - Moffett BS
AD  - Department of Pharmacy, Texas Children's Hospital, Houston, Texas, USA.
AD  - Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
FAU - Ivaturi, Vijay
AU  - Ivaturi V
AUID- ORCID: 0000-0002-6433-1154
AD  - Center for Translational Medicine, Department of Pharmacy Practice, University of 
      Maryland School of Pharmacy, Baltimore, Maryland, USA.
FAU - Gopalakrishnan, Mathangi
AU  - Gopalakrishnan M
AUID- ORCID: 0000-0003-2881-9870
AD  - Center for Translational Medicine, Department of Pharmacy Practice, University of 
      Maryland School of Pharmacy, Baltimore, Maryland, USA.
LA  - eng
PT  - Journal Article
DEP - 20220112
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Anticoagulants)
RN  - 0 (Factor Xa Inhibitors)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anticoagulants/therapeutic use
MH  - Child
MH  - Factor Xa Inhibitors
MH  - *Heparin/therapeutic use
MH  - Humans
MH  - Infant
MH  - Partial Thromboplastin Time
MH  - *Pediatrics
MH  - Retrospective Studies
OTO - NOTNLM
OT  - UFH
OT  - aPTT
OT  - anti-factor Xa
OT  - pediatrics
OT  - population PK/PD
EDAT- 2021/11/25 06:00
MHDA- 2022/04/30 06:00
CRDT- 2021/11/24 06:45
PHST- 2021/08/25 00:00 [received]
PHST- 2021/11/19 00:00 [accepted]
PHST- 2021/11/25 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2021/11/24 06:45 [entrez]
AID - 10.1002/jcph.2007 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2022 Jun;62(6):733-746. doi: 10.1002/jcph.2007. Epub 2022 Jan 
      12.