PMID- 17096680
OWN - NLM
STAT- MEDLINE
DCOM- 20070928
LR  - 20221207
IS  - 0306-5251 (Print)
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 63
IP  - 5
DP  - 2007 May
TI  - A mechanism-based binding model for the population pharmacokinetics and 
      pharmacodynamics of omalizumab.
PG  - 548-61
AB  - AIM: Omalizumab, a humanized IgG monoclonal antibody that binds to human 
      immunoglobulin E (IgE), interrupts the allergic cascade in asthmatic patients. 
      The aim was to compare simultaneously drug exposure and IgE biomarker responses 
      in Japanese and White patient populations. METHODS: An instantaneous equilibrium 
      drug-ligand binding and turnover population model was built from 202 Japanese 
      patients. A posterior predictive evaluation for the steady-state distributions of 
      omalizumab and IgE was then carried out against 531 White patients. RESULTS: The 
      mean parameters estimated from the Japanese patients were as follows: omalizumab 
      clearance 7.32 +/- 0.153 ml h(-1), IgE clearance 71.0 +/- 4.68 ml h(-1) and the 
      difference between that for omalizumab and the complex 5.86 +/- 0.920 ml h(-1), 
      the volume of distribution for omalizumab and IgE 5900 +/- 107 ml, and that for 
      the complex 3630 +/- 223 ml, the rate of IgE production 30.3 +/- 2.04 microg 
      h(-1). Half-lives of IgG (23 days) and IgE (2.4 days) were close to previous 
      reports. The dissociation constant for binding, 1.07 nM, was similar to in vitro 
      values. Clearance and volume of distribution for omalizumab varied with 
      bodyweight, whereas the clearance and rate of production of IgE were predicted 
      accurately by baseline IgE. Overall, these covariates explained much of the 
      interindividual variability. CONCLUSIONS: The predictiveness of the Japanese 
      model was confirmed by Monte-Carlo simulations for a White population, also 
      providing evidence that the pharmacokinetics of omalizumab and IgE were similar 
      in these two populations. Furthermore, the model enabled the estimation of not 
      only omalizumab disposition parameters, but also the binding with and the rate of 
      production, distribution and elimination of its target, IgE.
FAU - Hayashi, Naoto
AU  - Hayashi N
AD  - Drug Metabolism and Pharmacokinetics, Novartis Pharma AG, Basel, Switzerland.
FAU - Tsukamoto, Yuko
AU  - Tsukamoto Y
FAU - Sallas, William M
AU  - Sallas WM
FAU - Lowe, Philip J
AU  - Lowe PJ
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Validation Study
DEP - 20061110
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunoglobulin G)
RN  - 2P471X1Z11 (Omalizumab)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Anti-Asthmatic Agents/administration & dosage/*blood
MH  - Antibodies, Anti-Idiotypic
MH  - Antibodies, Monoclonal/administration & dosage/*blood
MH  - Antibodies, Monoclonal, Humanized
MH  - Asian People
MH  - Body Weight
MH  - Dose-Response Relationship, Drug
MH  - Half-Life
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Immunoglobulin G/blood
MH  - *Models, Biological
MH  - Monte Carlo Method
MH  - Omalizumab
MH  - White People
PMC - PMC2000760
EDAT- 2006/11/14 09:00
MHDA- 2007/09/29 09:00
PMCR- 2008/05/01
CRDT- 2006/11/14 09:00
PHST- 2006/11/14 09:00 [pubmed]
PHST- 2007/09/29 09:00 [medline]
PHST- 2006/11/14 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - BCP2803 [pii]
AID - 10.1111/j.1365-2125.2006.02803.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2007 May;63(5):548-61. doi: 
      10.1111/j.1365-2125.2006.02803.x. Epub 2006 Nov 10.