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Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants

Chung, Jou Ku ; Hallberg, Boubou ; Hansen-Pupp, Ingrid LU orcid ; Graham, Martin A. ; Fetterly, Gerald ; Sharma, Jyoti ; Tocoian, Adina ; Kreher, Nerissa C. ; Barton, Norman W. and Hellström, Ann LU , et al. (2017) In Pediatric Research 81(3). p.504-510
Abstract

Background:rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy of prematurity in extremely preterm infants.Methods:A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 μg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants... (More)

Background:rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy of prematurity in extremely preterm infants.Methods:A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 μg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants to verify dosing.Results:Serum IGF-1 data were reviewed for 10 treated/9 control infants. Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before infusion and <24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) μg/l (treated) and 15.4 (4.7) μg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) μg/l at 12 h in treated infants, and remained within target levels for all subsequent timepoints. For treated infants, 88.8% of the IGF-1 measurements were within target levels (controls, 11.1%).Conclusion:Through the reported work, we determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological intrauterine serum IGF-1 levels in extremely preterm infants.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
rhIGF-1/rhIGFBP-3, physiologic replacement, pharmacokinetic model
in
Pediatric Research
volume
81
issue
3
pages
7 pages
publisher
International Pediatric Foundation Inc.
external identifiers
  • scopus:85016396576
  • pmid:27870826
  • pmid:27870826
  • wos:000396297000023
ISSN
0031-3998
DOI
10.1038/pr.2016.255
language
English
LU publication?
yes
id
a1ebf7b1-eed2-4685-91e8-fc71a6411ba1
date added to LUP
2017-04-24 09:49:10
date last changed
2024-05-26 14:12:03
@article{a1ebf7b1-eed2-4685-91e8-fc71a6411ba1,
  abstract     = {{<p>Background:rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy of prematurity in extremely preterm infants.Methods:A population pharmacokinetic model was developed using data from phase I/II (Sections A-C) trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict optimal dosing to establish/maintain serum IGF-1 within physiological intrauterine levels. In Section D of the phase II study, infants (gestational age (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at the model-predicted dose of 250 μg/kg/d continuous i.v. infusion up to postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic analysis was performed for the first 10 treated infants to verify dosing.Results:Serum IGF-1 data were reviewed for 10 treated/9 control infants. Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before infusion and &lt;24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) μg/l (treated) and 15.4 (4.7) μg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) μg/l at 12 h in treated infants, and remained within target levels for all subsequent timepoints. For treated infants, 88.8% of the IGF-1 measurements were within target levels (controls, 11.1%).Conclusion:Through the reported work, we determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological intrauterine serum IGF-1 levels in extremely preterm infants.</p>}},
  author       = {{Chung, Jou Ku and Hallberg, Boubou and Hansen-Pupp, Ingrid and Graham, Martin A. and Fetterly, Gerald and Sharma, Jyoti and Tocoian, Adina and Kreher, Nerissa C. and Barton, Norman W. and Hellström, Ann and Ley, David}},
  issn         = {{0031-3998}},
  keywords     = {{rhIGF-1/rhIGFBP-3; physiologic replacement; pharmacokinetic model}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  pages        = {{504--510}},
  publisher    = {{International Pediatric Foundation Inc.}},
  series       = {{Pediatric Research}},
  title        = {{Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants}},
  url          = {{http://dx.doi.org/10.1038/pr.2016.255}},
  doi          = {{10.1038/pr.2016.255}},
  volume       = {{81}},
  year         = {{2017}},
}