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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 ; 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
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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
  • wos:000396297000023
ISSN
0031-3998
DOI
10.1038/pr.2016.255
language
English
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yes
id
a1ebf7b1-eed2-4685-91e8-fc71a6411ba1
date added to LUP
2017-04-24 09:49:10
date last changed
2018-01-07 12:00:32
@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},
  keyword      = {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},
  volume       = {81},
  year         = {2017},
}