PMID- 34741102
OWN - NLM
STAT- MEDLINE
DCOM- 20220419
LR  - 20240407
IS  - 1476-5543 (Electronic)
IS  - 0743-8346 (Print)
IS  - 0743-8346 (Linking)
VI  - 42
IP  - 1
DP  - 2022 Jan
TI  - Safety of sildenafil in extremely premature infants: a phase I trial.
PG  - 31-36
LID - 10.1038/s41372-021-01261-w [doi]
AB  - OBJECTIVE: To characterize the safety of sildenafil in premature infants. STUDY 
      DESIGN: A phase I, open-label trial of sildenafil in premature infants receiving 
      sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of 
      sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), 
      transaminase levels, and mean arterial pressure monitoring. RESULTS: Twenty-four 
      infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants 
      received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg 
      (n = 2). In cohort 2, there was one serious AE related to study drug involving 
      hypotension associated with a faster infusion rate than specified by the 
      protocol. There were no AEs related to elevated transaminases. CONCLUSION: 
      Sildenafil was well tolerated by the study population. Drug administration times 
      and flush rates require careful attention to prevent infusion-related hypotension 
      associated with faster infusions of IV sildenafil in premature infants. CLINICAL 
      TRIAL: ClinicalTrials.gov Identifier: NCT01670136.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Jackson, Wesley
AU  - Jackson W
AUID- ORCID: 0000-0002-9403-381X
AD  - Department of Pediatrics, School of Medicine, The University of North Carolina at 
      Chapel Hill, Chapel Hill, NC, USA. wesley.jackson@unc.edu.
FAU - Gonzalez, Daniel
AU  - Gonzalez D
AD  - Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of 
      Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
FAU - Smith, P Brian
AU  - Smith PB
AD  - Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
AD  - Duke Clinical Research Institute, Durham, NC, USA.
FAU - Ambalavanan, Namasivayam
AU  - Ambalavanan N
AUID- ORCID: 0000-0003-0731-9092
AD  - Division of Neonatology, School of Medicine, University of Alabama at Birmingham, 
      Birmingham, AL, USA.
FAU - Atz, Andrew M
AU  - Atz AM
AD  - Department of Pediatrics, Medical University of South Carolina Children's 
      Hospital, Charleston, SC, USA.
FAU - Sokol, Gregory M
AU  - Sokol GM
AUID- ORCID: 0000-0002-2917-1423
AD  - Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, 
      Indianapolis, IN, USA.
FAU - Hornik, Chi D
AU  - Hornik CD
AD  - Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
AD  - Duke Clinical Research Institute, Durham, NC, USA.
FAU - Stewart, Dan
AU  - Stewart D
AUID- ORCID: 0000-0003-4026-9226
AD  - University of Louisville Norton Children's Hospital, Louisville, KY, USA.
FAU - Mundakel, Gratias
AU  - Mundakel G
AD  - Kings County Hospital Center/SUNY Downstate Medical Center, Brooklyn, NY, USA.
FAU - Poindexter, Brenda B
AU  - Poindexter BB
AD  - Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, 
      Atlanta, GA, USA.
FAU - Ahlfeld, Shawn K
AU  - Ahlfeld SK
AD  - Department of Pediatrics, University of Cincinnati College of Medicine, 
      Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
FAU - Mills, Mary
AU  - Mills M
AD  - Duke Clinical Research Institute, Durham, NC, USA.
FAU - Cohen-Wolkowiez, Michael
AU  - Cohen-Wolkowiez M
AD  - Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
AD  - Duke Clinical Research Institute, Durham, NC, USA.
FAU - Martz, Karen
AU  - Martz K
AD  - The Emmes Company, LLC, Rockville, MD, USA.
FAU - Hornik, Christoph P
AU  - Hornik CP
AD  - Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
AD  - Duke Clinical Research Institute, Durham, NC, USA.
FAU - Laughon, Matthew M
AU  - Laughon MM
AUID- ORCID: 0000-0002-4052-3215
AD  - Department of Pediatrics, School of Medicine, The University of North Carolina at 
      Chapel Hill, Chapel Hill, NC, USA.
CN  - Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee
LA  - eng
SI  - ClinicalTrials.gov/NCT01670136
GR  - HHSN275201000003C/AA/NIAAA NIH HHS/United States
GR  - HHSN275201000003I/HD/NICHD NIH HHS/United States
GR  - K24 HL143283/HL/NHLBI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20211105
PL  - United States
TA  - J Perinatol
JT  - Journal of perinatology : official journal of the California Perinatal 
      Association
JID - 8501884
RN  - BW9B0ZE037 (Sildenafil Citrate)
SB  - IM
MH  - Humans
MH  - *Hypotension/chemically induced/drug therapy
MH  - Infant, Extremely Premature
MH  - Infant, Low Birth Weight
MH  - Infant, Newborn
MH  - *Infant, Premature, Diseases/drug therapy
MH  - Sildenafil Citrate/adverse effects
PMC - PMC8569839
COIS- The authors declare no competing interests.
EDAT- 2021/11/07 06:00
MHDA- 2022/04/20 06:00
PMCR- 2021/11/05
CRDT- 2021/11/06 06:03
PHST- 2021/08/03 00:00 [received]
PHST- 2021/10/20 00:00 [accepted]
PHST- 2021/10/16 00:00 [revised]
PHST- 2021/11/07 06:00 [pubmed]
PHST- 2022/04/20 06:00 [medline]
PHST- 2021/11/06 06:03 [entrez]
PHST- 2021/11/05 00:00 [pmc-release]
AID - 10.1038/s41372-021-01261-w [pii]
AID - 1261 [pii]
AID - 10.1038/s41372-021-01261-w [doi]
PST - ppublish
SO  - J Perinatol. 2022 Jan;42(1):31-36. doi: 10.1038/s41372-021-01261-w. Epub 2021 Nov 
      5.