PMID- 32575458
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2073-4468 (Electronic)
IS  - 2073-4468 (Linking)
VI  - 9
IP  - 2
DP  - 2020 Jun 19
TI  - Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic 
      Evidence.
LID - 10.3390/antib9020024 [doi]
LID - 24
AB  - Immunoglobulins (IGs) are widely used for the treatment of immunodeficiency 
      syndromes and several autoimmune diseases. In neonates, IGs have been used for 
      the treatment of alloimmune thrombocytopenia, in neonatal infections and in the 
      rare cases of neonatal Kawasaki disease. This review aims to examine the various 
      dosing regimens of IGs following intravenous (IV) and subcutaneous (SC) 
      administration, pharmacokinetics (PK) of IGs, and the importance of trough values 
      for the prevention of infections in patients with primary immune deficiency 
      (PID). The review also focuses on the mechanism of catabolism of IGs and the 
      impact on the half-life of IGs. Data and reviews were obtained from the 
      literature and the FDA package inserts. The authors suggest that for dosing, the 
      PK of IGs should be evaluated on the baseline-corrected concentrations since this 
      approach provides an accurate estimate of half-life and clearance of IGs. We also 
      suggest employing clearance as a primary PK parameter for dosing determination of 
      IGs. We suggest that IV dosing would be more effective if given more frequently 
      to adjust for the increased clearance at high doses and because the 
      baseline-corrected half-life is much shorter than the baseline-uncorrected 
      half-life. Regarding SC administration, the dose should be adjusted based on the 
      absolute bioavailability (determined against IV dosing) of the product. Finally, 
      we highlight clinical and PK data gaps for optimum and individualized dosing of 
      IGs.
FAU - Mahmood, Iftekhar
AU  - Mahmood I
AD  - Division of Clinical Evaluation and Pharmacology/Toxicology, Office of Tissue and 
      Advanced Therapies (OTAT), Center for Biologics Evaluation and Research (CBER), 
      Food & Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 
      20993, USA.
FAU - Tegenge, Million A
AU  - Tegenge MA
AD  - Office of Biostatistics & Epidemiology, Center for Biologics Evaluation and 
      Research (CBER), Food & Drug Administration (FDA), 10903 New Hampshire Avenue, 
      Silver Spring, MD 20993, USA.
FAU - Golding, Basil
AU  - Golding B
AD  - Division of Plasma Protein Therapeutics, Office of Tissue and Advanced Therapies 
      (OTAT), Center for Biologics Evaluation and Research (CBER), Food & Drug 
      Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, 
      USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200619
PL  - Switzerland
TA  - Antibodies (Basel)
JT  - Antibodies (Basel, Switzerland)
JID - 101587489
PMC - PMC7345246
OTO - NOTNLM
OT  - clearance
OT  - dose
OT  - half-life
OT  - immunoglobulins
OT  - neonates
OT  - primary immune deficiency
COIS- The authors declare no conflict of interest.
EDAT- 2020/06/25 06:00
MHDA- 2020/06/25 06:01
PMCR- 2020/06/19
CRDT- 2020/06/25 06:00
PHST- 2020/05/19 00:00 [received]
PHST- 2020/06/07 00:00 [revised]
PHST- 2020/06/17 00:00 [accepted]
PHST- 2020/06/25 06:00 [entrez]
PHST- 2020/06/25 06:00 [pubmed]
PHST- 2020/06/25 06:01 [medline]
PHST- 2020/06/19 00:00 [pmc-release]
AID - antib9020024 [pii]
AID - antibodies-09-00024 [pii]
AID - 10.3390/antib9020024 [doi]
PST - epublish
SO  - Antibodies (Basel). 2020 Jun 19;9(2):24. doi: 10.3390/antib9020024.