Population Pharmacokinetic Model of Sublingual Buprenorphine in Neonatal Abstinence Syndrome. Issue 7 (14th July 2015)

• Record Type: Journal Article
• Authors: Ng, Chee M.; Dombrowsky, Erin; Lin, Hopi; Erlich, Michelle E.; Moody, David E.; Barrett, Jeffrey S.; Kraft, Walter K.
• Is Part Of: Pharmacotherapy. Volume 35:Issue 7(2015)
• Page Start: 670
• Page End: 680
• Publication Date: 2015-07-14
• Subjects: Chemotherapy -- Periodicals; Pharmacology -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1002/phar.1610
• Languages: English
• ISSNs: 0277-0008

Abstract

<abstract abstract-type="main" id="phar1610-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="phar1610-sec-0001" sec-type="section"> <title>Objective</title> <p>Neonatal abstinence syndrome (NAS)—a clinical entity of infants from <italic>in utero</italic> exposure to psychoactive xenobiotic and buprenorphine—has been successfully used to treat NAS. However, nothing is known about the pharmacokinetics (PK) of buprenorphine in neonates with NAS. To our knowledge, this is the first study to investigate the population pharmacokinetic of sublingual buprenorphine in neonates with NAS.</p> </sec> <sec id="phar1610-sec-0002" sec-type="section"> <title>Design</title> <p>A retrospective population PK analysis of: (1) neonates with NAS treated with sublingual buprenorphine in randomized, double blinded clinical study and (2) data from healthy adults from a previously published pharmacokinetic study.</p> </sec> <sec id="phar1610-sec-0003" sec-type="section"> <title>Setting</title> <p>Neonatal intensive care unit and general clinical research unit.</p> </sec> <sec id="phar1610-sec-0004" sec-type="section"> <title>Patients</title> <p>Twenty‐four neonates with NAS and five healthy adults.</p> </sec> <sec id="phar1610-sec-0005" sec-type="section"> <title>Interventions</title> <p>All participants received sublingual buprenorphine per study protocol.</p> </sec> <sec id="phar1610-sec-0006" sec-type="section"> <title>Measurements and Main Results</title> <p>A total of 303 PK data from 29 neonates and adults were used for model development. A population pharmacokinetic analysis was conducted using a first order conditional estimation with interaction in the NONMEM software program. A two‐compartment linear PK model with first‐order absorption process best described the pharmacokinetics of sublingual buprenorphine in neonates. The apparent clearance (CL) of buprenorphine was linearly related to body weight and matured with increasing age via two distinct saturated pathways. A typical neonate with NAS (body weight, 2.9 kg; postnatal age; 5.4 days) had a CL of 3.5 L/kg/hour and elimination half‐life of 11 hours. Phenobarbital did not affect the clearance of buprenorphine compared to neonates of similar age and weight.</p> </sec> <sec id="phar1610-sec-0007" sec-type="section"> <title>Conclusions</title> <p>This is the first study to investigate the population PK of sublingual buprenorphine in neonatal NAS. To our knowledge, this is also the first report to describe the age‐dependent changes of buprenorphine PK in this patient population. No buprenorphine dose adjustment is needed for neonates with NAS treated with buprenorphine and concurrent phenobarbital.</p> </sec> </abstract>