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This is significant because perinatal use of morphine has the potential for neurodevelopmental consequences. Still, the clonidine group reached symptom stabilization (Finnegan score (FS)\u2009&lt;\u20098) later than the morphine group and had a more significant number of patients who required adjunct therapy. However, the mean FS was consistently lower in the clonidine group after day 6. This prompted us to use pharmacokinetic (PK) and parametric time\u2010to\u2010event (TTE) modeling to simulate dosage schedules that may decrease the time to stabilization and reduce the need for adjunct therapy. Population PK (popPK) analysis was conducted, and the final model was a one\u2010compartment model with first\u2010order absorption and elimination, incorporating allometric scaling and age effect on apparent clearance (CL\/F) and apparent volume (V\/F). The population estimates for CL\/F and V\/F were 13.6\u2009L\/h\/70\u2009kg and 416\u2009L\/70\u2009kg, respectively, similar to the reported values. A Weibull model described the TTE data best, followed by incorporating predicted average concentrations to yield the final Weibull accelerated failure time model. Simulations of dosing strategies showed that increasing both the starting and maximum doses could potentially shorten the time to stabilization, and thus, length of treatment and hospital stay. Given the hypothesis\u2010generating nature of this analysis, the recommended dosing regimens should be tested prospectively to evaluate their benefits.<\/jats:p>","DOI":"10.1002\/cpt.3507","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T10:14:41Z","timestamp":1732270481000},"page":"1254-1263","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetic Modeling and Model\u2010Based Hypothesis Generation for Dose Optimization of Clonidine in Neonates With Neonatal Opioid Withdrawal Syndrome"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-7569","authenticated-orcid":false,"given":"Fei","family":"Tang","sequence":"first","affiliation":[{"name":"Genentech, Inc.  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