Considerations for pharmacokinetic assessment of immunoglobulins: Gammagard in very low birth weight neonates with and without baseline-correction.
Gammagard
Immunoglobulins
Neonates
Pharmacokinetics
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
02 Mar 2020
02 Mar 2020
Historique:
received:
14
01
2020
revised:
16
02
2020
accepted:
26
02
2020
pubmed:
7
3
2020
medline:
7
3
2020
entrez:
6
3
2020
Statut:
aheadofprint
Résumé
Immunoglobulins are widely used across multiple therapeutic areas such as immunodeficiency syndromes, infection and autoimmune diseases. The pharmacokinetics (PK) of immunoglobulins are well characterized in adults, but very little is known about the PK of immunoglobulins in neonates and infants. The objective of the present study was to characterize the PK of Gammagard, an immunoglobulin, in very low birth weight preterm neonates. Gammagard concentration-time data from very low birth weight neonates (bodyweight range 0.78-1.38 kg, n = 20) following intravenous administration of 500 mg/kg and 750 mg/kg were obtained from the literature. The data were analyzed with and without baseline correction using extensive blood samples (8 blood samples). Model-independent (non-compartmental) analysis was used to characterize the PK of Gammagard. Based on uncorrected baseline concentration-time data, the clearance and half-life of Gammagard were 3.1 ± 0.7 mL/day and 22 ± 6 days, respectively. Based on corrected baseline concentration-time data, the clearance and half-life of Gammagard were 20.2 ± 7.4 mL/day and 5.3 ± 2.2 days, respectively. The dose of immunoglobulins should be adjusted based on the PK of baseline corrected rather than baseline uncorrected profiles because baseline corrected PK parameters especially half-life reconciles with PK principles.
Sections du résumé
BACKGROUND
BACKGROUND
Immunoglobulins are widely used across multiple therapeutic areas such as immunodeficiency syndromes, infection and autoimmune diseases. The pharmacokinetics (PK) of immunoglobulins are well characterized in adults, but very little is known about the PK of immunoglobulins in neonates and infants.
OBJECTIVE
OBJECTIVE
The objective of the present study was to characterize the PK of Gammagard, an immunoglobulin, in very low birth weight preterm neonates.
METHOD
METHODS
Gammagard concentration-time data from very low birth weight neonates (bodyweight range 0.78-1.38 kg, n = 20) following intravenous administration of 500 mg/kg and 750 mg/kg were obtained from the literature. The data were analyzed with and without baseline correction using extensive blood samples (8 blood samples). Model-independent (non-compartmental) analysis was used to characterize the PK of Gammagard.
RESULTS
RESULTS
Based on uncorrected baseline concentration-time data, the clearance and half-life of Gammagard were 3.1 ± 0.7 mL/day and 22 ± 6 days, respectively. Based on corrected baseline concentration-time data, the clearance and half-life of Gammagard were 20.2 ± 7.4 mL/day and 5.3 ± 2.2 days, respectively.
CONCLUSION
CONCLUSIONS
The dose of immunoglobulins should be adjusted based on the PK of baseline corrected rather than baseline uncorrected profiles because baseline corrected PK parameters especially half-life reconciles with PK principles.
Identifiants
pubmed: 32135491
pii: S1567-5769(20)30132-6
doi: 10.1016/j.intimp.2020.106358
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106358Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflict of interest.