Abstract | AIM: METHODS: Near-term neonates, born in Kinshasa, Democratic Republic of Congo, with a Thompson score ≥ 7 were eligible for inclusion. Excluded were patients with (1) inability to insert an umbilical venous catheter for administration of the study drug; (2) major congenital or chromosomal abnormalities; (3) birth weight < 1800 g; (4) clear signs of infection; and (5) moribund patients. Neonates received six infusions of 2-iminobiotin 0.16 mg/kg started within 6 h after birth, with 4-h intervals, targeting an AUC0-4h of 365 ng*h/mL. Safety, defined as vital signs, the need for clinical intervention after administration of study drug, occurrence of (serious) adverse events, and pharmacokinetics were assessed. RESULTS: After parental consent, seven patients were included with a median Thompson score of 10 (range 8-16). No relevant changes in vital signs were observed over time. There was no need for clinical intervention due to administration of study drug. Three patients died, two after completing the study protocol, one was moribund at inclusion and should not have been included. Pharmacokinetic data of 2-iminobiotin were best described using a two-compartment model. Median AUC0-4h was 664 ng*h/mL (range 414-917). No safety issues attributed to the administration of 2-iminobiotin were found. CONCLUSION: The present dosing regimen resulted in higher AUCs than targeted, necessitating a change in the dose regimen in future efficacy trials. No adverse effects that could be attributed to the use of 2-iminobiotin were observed. EudraCT number 2015-003063-12.
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Authors | Thérèse Biselele, Jephté Bambi, Dieu M Betukumesu, Yoly Ndiyo, Gabriel Tabu, Josée Kapinga, Valérie Bola, Pascal Makaya, Huibert Tjabbes, Peter Vis, Cacha Peeters-Scholte |
Journal | Paediatric drugs
(Paediatr Drugs)
Vol. 22
Issue 1
Pg. 95-104
(Feb 2020)
ISSN: 1179-2019 [Electronic] Switzerland |
PMID | 31960360
(Publication Type: Clinical Trial, Phase II, Journal Article)
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Chemical References |
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Topics |
- Adult
- Asphyxia
(drug therapy)
- Biotin
(analogs & derivatives, pharmacology, therapeutic use)
- Female
- Humans
- Infant, Newborn
- Male
- Poverty
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