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Poster presented at 2009 American College of Clinical Pharmacology conference in Orlando. April 24-28.

Background: About 55 to 94% of infants born to opioid dependent mothershave neonatal abstinence syndrome (NAS). Buprenorphine (BUP) is usedclinically as an analgesic and a detoxification agent and a maintenancetreatment for opioid dependence. No data, however, has been reported about the use of sublingual administration of BUP below the age of 4 year, especially for term infants with NAS.

Objectives: Characterize pharmacokinetics (PK) of BUP in newborn patients;Evaluate the developmental changes in newborns in order to assist dosingoptimization in ongoing clinical studies.

Methods: In silico prediction of PK behavior and physiological development in newborn patients were evaluated using SIMCYP. Intravenous clearance was predicted through physiologically based simulation method in SIMCYP. Basedon sublingual clearance obtained from a one compartmental model developedpreviously using NONMEM, individual changes of sublingual bioavailability were evaluated with physiological development in the first one and half month during the newborn period.

Results: Intrinsic clearance of BUP in newborns were incorporated into enzymekinetic data obtained from literature. Change of sublingual bioavailability fornewborns was evaluated with bioavailability-postmenstrual age profiles.Sublingual bioavailability of BUP was estimated as 8.9--56.6% in newborn patients studied during the first one and half postnatal month.

Conclusion: Developmental considerations for the PK of BUP in newborns are important for the characterization of the dose-exposure relationship. We have evaluated this from “bottom-up” and “top-down” approaches with SIMCYP and NONMEM respectively and found these approaches to be complementary andvaluable for clinical trial design and routine clinical care. Presumably theywould facilitate rational decision making in pediatric drug development as well.



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