PMID- 35860862
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20230227
IS  - 2163-8306 (Electronic)
IS  - 2163-8306 (Linking)
VI  - 11
IP  - 10
DP  - 2022 Oct
TI  - Physiologically-based pharmacokinetic modeling of immunoglobulin and antibody 
      coadministration in patients with primary human immunodeficiency.
PG  - 1316-1327
LID - 10.1002/psp4.12847 [doi]
AB  - Intravenous immunoglobulin (IVIG) (2000 mg/kg) increased the clearance of the 
      mouse monoclonal antibody 7E3, directed against platelet integrin IIb/IIIa (alpha 
      IIb beta 3, CD41/CD61) in rodents. We wanted to investigate the effect of IVIG on 
      clearance of monoclonal antibodies in humans as there is extremely limited data 
      regarding this interaction in the literature. Using the tyrosine protein kinase 
      KIT anti-cluster of differentiation 117 (c-Kit) humanized monoclonal antibody 
      (JSP191) as a case study, we used physiologically-based pharmacokinetic (PBPK) 
      modeling to evaluate the pharmacokinetic interaction between monoclonal 
      antibodies and IVIG at doses (300-600 mg/kg) administered to patients with 
      primary human immunodeficiency (PI). We first characterized the interaction 
      between monoclonal antibodies and IVIG in PK-Sim(R)/MoBi(R) using published 
      literature data, including the following: IVIG plus 7E3 in mice and rats and IVIG 
      plus the human anti-C5 monoclonal antibody tesidolumab in adults with end-stage 
      renal disease. We next developed a PBPK model using digitized data for JSPI91 
      alone in older adults with myelodysplastic syndrome and acute myeloid leukemia 
      and in pediatric patients with severe combined immunodeficiency (SCID). Finally, 
      we simulated the impact of IVIG (300-2000 mg/kg) coadministration with JSP191 on 
      the area under the curve of JSP191 in patients with SCID. Model predictions were 
      within 1.5-fold of observed values for 7E3 plus IVIG and tesidolumab plus IVIG as 
      well as for JSP191 administered alone. Based on our simulations, IVIG doses 
      >/=500 mg exceeded the 80%-125% no-effect boundaries. IVIG treatment with 
      monoclonal antibodies in patients with PI may result in a clinically significant 
      interaction depending on the IVIG dose administered and the exposure-response 
      relationship for the specific monoclonal antibody.
CI  - (c) 2022 Gilead. CPT: Pharmacometrics & Systems Pharmacology published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Salerno, Sara N
AU  - Salerno SN
AUID- ORCID: 0000-0002-8884-2127
AD  - Gilead Sciences, Inc., Foster City, California, USA.
FAU - Deng, Rong
AU  - Deng R
AD  - Gilead Sciences, Inc., Foster City, California, USA.
AD  - R&D Q-Pharm Consulting LLC, Pleasanton, California, USA.
FAU - Kakkar, Tarundeep
AU  - Kakkar T
AD  - Gilead Sciences, Inc., Foster City, California, USA.
LA  - eng
PT  - Journal Article
DEP - 20220808
PL  - United States
TA  - CPT Pharmacometrics Syst Pharmacol
JT  - CPT: pharmacometrics & systems pharmacology
JID - 101580011
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Integrins)
RN  - 3FO6689MSD (tesidolumab)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Aged
MH  - Animals
MH  - *Antibodies, Monoclonal
MH  - Antibodies, Monoclonal, Humanized
MH  - Child
MH  - Humans
MH  - *Immunoglobulins, Intravenous/therapeutic use
MH  - Integrins
MH  - Mice
MH  - Protein-Tyrosine Kinases
MH  - Rats
PMC - PMC9574734
COIS- Sara N. Salerno and Tarundeep Kakkar are employees at Gilead and receive stock 
      options. Rong Deng is a paid consultant for Gilead.
EDAT- 2022/07/22 06:00
MHDA- 2022/10/19 06:00
PMCR- 2022/10/01
CRDT- 2022/07/21 02:52
PHST- 2022/05/26 00:00 [revised]
PHST- 2022/03/11 00:00 [received]
PHST- 2022/06/29 00:00 [accepted]
PHST- 2022/07/22 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/07/21 02:52 [entrez]
PHST- 2022/10/01 00:00 [pmc-release]
AID - PSP412847 [pii]
AID - 10.1002/psp4.12847 [doi]
PST - ppublish
SO  - CPT Pharmacometrics Syst Pharmacol. 2022 Oct;11(10):1316-1327. doi: 
      10.1002/psp4.12847. Epub 2022 Aug 8.