Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome.

Publication/Presentation Date

11-1-2021

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 (EC

Volume

14

Issue

6

First Page

2171

Last Page

2183

ISSN

1752-8062

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

34080312

Department(s)

Administration and Leadership

Document Type

Article

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