PMID- 25497995
OWN - NLM
STAT- MEDLINE
DCOM- 20150902
LR  - 20151119
IS  - 1096-0295 (Electronic)
IS  - 0273-2300 (Linking)
VI  - 71
IP  - 1
DP  - 2015 Feb
TI  - Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for 
      specific ranges of bodyweight and baseline IgE.
PG  - 68-77
LID - S0273-2300(14)00295-5 [pii]
LID - 10.1016/j.yrtph.2014.12.002 [doi]
AB  - The dosing level and frequency of omalizumab are guided by a dosing table based 
      on total serum immunoglobulin E (IgE) and bodyweight. Using a validated, 
      mathematical simulation model (based on concentration data from 8 studies), we 
      evaluated the impact of a revised omalizumab dosing table (every 4 weeks dosing 
      regimen) on the pharmacokinetic and pharmacodynamic profiles of free and total 
      IgE. Safety analysis, in patients with high levels of exposure to omalizumab, was 
      done using data from the clinical and post-marketing databases. The model 
      accurately predicted observed omalizumab, free and total IgE concentrations. 
      After reaching steady-state, the average increase in exposure was 10%, even for 
      patients with the highest concentrations at the upper 97.5th percentile. Free IgE 
      suppression slightly increased in the initial phase, and slightly reduced at the 
      trough of the dosing cycle, but average suppression remained similar for both 
      regimens. The safety profile of omalizumab was similar for patients receiving 
      higher or lower doses. Thus, doubling the dose of omalizumab, in a subset of 
      patients receiving 225-300 mg of omalizumab (every 2 weeks dosing regimen) can 
      efficiently suppress free IgE without compromising safety or efficacy.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Lowe, Philip J
AU  - Lowe PJ
AD  - Novartis Pharma AG, Basel, Switzerland. Electronic address: 
      phil.lowe@novartis.com.
FAU - Georgiou, Panayiotis
AU  - Georgiou P
AD  - Novartis Pharmaceuticals UK Limited, Horsham, West Sussex, UK.
FAU - Canvin, Janice
AU  - Canvin J
AD  - Novartis Pharmaceuticals UK Limited, Horsham, West Sussex, UK.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20141208
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 2P471X1Z11 (Omalizumab)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anti-Asthmatic Agents/*administration & 
      dosage/blood/pharmacokinetics/pharmacology
MH  - Antibodies, Anti-Idiotypic/*administration & dosage/blood/pharmacology
MH  - Antibodies, Monoclonal, Humanized/*administration & 
      dosage/blood/pharmacokinetics/pharmacology
MH  - Asthma/blood/drug therapy
MH  - Body Weight
MH  - Child
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Middle Aged
MH  - *Models, Biological
MH  - Omalizumab
MH  - Young Adult
OTO - NOTNLM
OT  - Allergic asthma
OT  - Anti-immunoglobulin E
OT  - Dosing table
OT  - Modeling and simulation
OT  - Omalizumab
EDAT- 2014/12/17 06:00
MHDA- 2015/09/04 06:00
CRDT- 2014/12/16 06:00
PHST- 2014/09/25 00:00 [received]
PHST- 2014/12/01 00:00 [revised]
PHST- 2014/12/02 00:00 [accepted]
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/09/04 06:00 [medline]
AID - S0273-2300(14)00295-5 [pii]
AID - 10.1016/j.yrtph.2014.12.002 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2015 Feb;71(1):68-77. doi: 10.1016/j.yrtph.2014.12.002. 
      Epub 2014 Dec 8.