Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome

Abstract Results from Blinded Buprenorphine OR Neonatal morphine solution (BBORN), a previous phase III trial in infants with neonatal opioid withdrawal syndrome (NOWS), demonstrated that sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than th...

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Autores principales:	Rena Eudy‐Byrne, Nicole Zane, Susan C. Adeniyi‐Jones, Marc R. Gastonguay, Ana Ruiz‐Garcia, Gagan Kushal, Walter K. Kraft
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/36acd5d7a6f74a369d135df943dae29b
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spelling	oai:doaj.org-article:36acd5d7a6f74a369d135df943dae29b2021-11-19T17:51:34ZPharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome1752-80621752-805410.1111/cts.13074https://doaj.org/article/36acd5d7a6f74a369d135df943dae29b2021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13074https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract Results from Blinded Buprenorphine OR Neonatal morphine solution (BBORN), a previous phase III trial in infants with neonatal opioid withdrawal syndrome (NOWS), demonstrated that sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than the comparator, oral morphine. Objectives of Buprenorphine Pharmacometric Open Label Research study of Drug Exposure (BPHORE), a new trial with buprenorphine in a similar population, were to (1) optimize initial dose, up‐titration to achieve symptom control and weaning steps of pharmacologic treatment and (2) investigate safety of the revised regimen. A pharmacodynamic model linked buprenorphine exposure to NOWS symptom scores. Adaptive dose regimens were simulated using BBORN results to compare dosing regimens for times to stabilization, weaning, and cessation. A clinical trial using model informed doses (BPHORE), was conducted. Simulations indicated benefits in time to stabilization and weaning when up‐titration rates increased to 30%. Stabilization time was not greatly impacted by the starting dose. Time to wean and time to cessation were dose dependent. A weaning rate of 25% shortened time to cessation. Ten infants were enrolled in BPHORE using buprenorphine starting dose of 24 µg/kg/day, 33% titration, and 15% wean rate. Five subjects required adjuvant therapy. Half‐maximal effective concentration (EC50) values indicated maximum buprenorphine doses did not generate maximal effect size, suggesting potential efficacy of a further increased dose if a goal was to reduce the use of adjunct agents. Simulations indicated that further benefits can be gained by increasing starting doses of buprenorphine and increasing wean rates. Use of a model‐based analysis to provide focused guidelines for care can be used with goals of reducing treatment time and hospital stays in infants with NOWS.Rena Eudy‐ByrneNicole ZaneSusan C. Adeniyi‐JonesMarc R. GastonguayAna Ruiz‐GarciaGagan KushalWalter K. KraftWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2171-2183 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Rena Eudy‐Byrne Nicole Zane Susan C. Adeniyi‐Jones Marc R. Gastonguay Ana Ruiz‐Garcia Gagan Kushal Walter K. Kraft Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome
description	Abstract Results from Blinded Buprenorphine OR Neonatal morphine solution (BBORN), a previous phase III trial in infants with neonatal opioid withdrawal syndrome (NOWS), demonstrated that sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than the comparator, oral morphine. Objectives of Buprenorphine Pharmacometric Open Label Research study of Drug Exposure (BPHORE), a new trial with buprenorphine in a similar population, were to (1) optimize initial dose, up‐titration to achieve symptom control and weaning steps of pharmacologic treatment and (2) investigate safety of the revised regimen. A pharmacodynamic model linked buprenorphine exposure to NOWS symptom scores. Adaptive dose regimens were simulated using BBORN results to compare dosing regimens for times to stabilization, weaning, and cessation. A clinical trial using model informed doses (BPHORE), was conducted. Simulations indicated benefits in time to stabilization and weaning when up‐titration rates increased to 30%. Stabilization time was not greatly impacted by the starting dose. Time to wean and time to cessation were dose dependent. A weaning rate of 25% shortened time to cessation. Ten infants were enrolled in BPHORE using buprenorphine starting dose of 24 µg/kg/day, 33% titration, and 15% wean rate. Five subjects required adjuvant therapy. Half‐maximal effective concentration (EC50) values indicated maximum buprenorphine doses did not generate maximal effect size, suggesting potential efficacy of a further increased dose if a goal was to reduce the use of adjunct agents. Simulations indicated that further benefits can be gained by increasing starting doses of buprenorphine and increasing wean rates. Use of a model‐based analysis to provide focused guidelines for care can be used with goals of reducing treatment time and hospital stays in infants with NOWS.
format	article
author	Rena Eudy‐Byrne Nicole Zane Susan C. Adeniyi‐Jones Marc R. Gastonguay Ana Ruiz‐Garcia Gagan Kushal Walter K. Kraft
author_facet	Rena Eudy‐Byrne Nicole Zane Susan C. Adeniyi‐Jones Marc R. Gastonguay Ana Ruiz‐Garcia Gagan Kushal Walter K. Kraft
author_sort	Rena Eudy‐Byrne
title	Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome
title_short	Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome
title_full	Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome
title_fullStr	Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome
title_full_unstemmed	Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome
title_sort	pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/36acd5d7a6f74a369d135df943dae29b
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Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome

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