The Pharmacokinetics and Pharmacodynamics of Buprenorphine in Neonatal Abstinence Syndrome

Moore, Jason N.; Gastonguay, Marc R.; Ng, Chee M.; Adeniyi-Jones, Susan; Moody, David E.; Fang, Wenfang B.; Ehrlich, Michelle E.; Kraft, Walter K.

doi:10.1002/cpt.1064

Cited by 31 publications

(36 citation statements)

References 27 publications

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“…Data from the phase III BBORN trial based on this structural model revealed similar results to that seen in the phase I trial. 56 Kamatkar et al . described the PK of buprenorphine in 63 samples from a cohort of 20 NAS infants treated at the University of Cincinnati in an open-label approach.…”

Section: Buprenorphine Pk/pd In Nasmentioning

confidence: 99%

“…This is supported by observations of 1) increased clearance associated with worse NAS symptoms, 2) more severe NAS generally requiring a higher AUC to control symptoms, and 3) that higher average concentrations of buprenorphine were correlated with faster time to stabilization. 56 Major covariates that drive this variability in drug exposure and clearance have not been identified. However, the linkage between exposure and response when combined with disease state models will allow future simulations to identify regimens more likely to control symptoms quickly and minimize duration of pharmacologic treatment.…”

Section: Buprenorphine Pk/pd In Nasmentioning

confidence: 99%

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Buprenorphine in Neonatal Abstinence Syndrome

Kraft

2017

Clin Pharma and Therapeutics

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Infants exposed in utero to opioids will demonstrate a withdrawal syndrome known as neonatal abstinence syndrome (NAS). Buprenorphine is a long‐acting opioid with therapeutic use in medication‐assisted treatment of opioid dependency in adults and adolescents. Emerging data from clinical trials and treatment cohorts demonstrate the efficacy and safety of sublingual buprenorphine for those infants with NAS who require pharmacologic treatment. Pharmacometric modeling will assist in defining the exposure–response relationships and facilitate dose optimization.

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Section: Buprenorphine Pk/pd In Nasmentioning

confidence: 99%

Section: Buprenorphine Pk/pd In Nasmentioning

confidence: 99%

Buprenorphine in Neonatal Abstinence Syndrome

Kraft

2017

Clin Pharma and Therapeutics

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“…The study used an indirect response model to assess the concentration‐response relationship between buprenorphine concentrations and Finnegan scores. Similarly, Moore et al 110 assessed the PK/PD relationship of neonates treated with buprenorphine for NOWS. The study predicted the PK of buprenorphine and its metabolite norbuprenorphine and used the MOTHER NAS Scale (a modified version of the Finnegan scoring system) to assess the PD of each neonate.…”

Section: Pharmacodynamics Of Opioids In Infants With Nowsmentioning

confidence: 99%

Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches

McPhail

Emoto

Butler

et al. 2021

The Journal of Clinical Pharma

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Chronic intrauterine exposure to psychoactive drugs often results in neonatal opioid withdrawal syndrome (NOWS). When nonpharmacologic measures are insufficient in controlling NOWS, morphine, methadone, and buprenorphine are first‐line medications commonly used to treat infants with NOWS because of in utero exposure to opioids. Research suggests that buprenorphine may be the leading drug therapy used to treat NOWS when compared with morphine and methadone. Currently, there are no consensus or standardized treatment guidelines for medications prescribed for NOWS. Opioids used to treat NOWS exhibit large interpatient variability in pharmacokinetics (PK) and pharmacodynamic (PD) response in neonates. Organ systems undergo rapid maturation after birth that may alter drug disposition and exposure for any given dose during development. Data regarding the PK and PD of opioids in neonates are sparse. Pharmacometric methods such as physiologically based pharmacokinetic and population pharmacokinetic modeling can be used to explore factors predictive of some of the variability associated with the PK/PD of opioids in newborns. This review discusses the utility of pharmacometric techniques for enhancing precision dosing in infants requiring opioid treatment for NOWS. Applying these approaches may contribute to optimizing the outcome by reducing cumulative drug exposure, mitigating adverse drug effects, and reducing the burden of NOWS in neonates.

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“…Because a growing number of pregnant opioid users receive buprenorphine maintenance therapy, concerns regarding the adverse effects of this long-lasting opioid on the brain function of offspring have received increasing attention [1][2][3][4]. Indeed, visuomotor dysfunction has been reported in children prenatally exposed to opioids [5].…”

Section: Introductionmentioning

confidence: 99%

Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine

Lin

Tao

Tsay³

et al. 2021

Behavioural Neurology

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Prenatal exposure to buprenorphine renders offspring vulnerable to cerebral impairments. In this study, our data demonstrate, for the first time, that prenatal exposure to buprenorphine escalates astrocyte activation concurrent with indications of endoplasmic reticulum (ER) stress in the hippocampi of neonates, and this can be prevented by the coadministration of dextromethorphan with buprenorphine. Furthermore, dextromethorphan can inhibit the accumulation of GPR37 in the hippocampus of newborns caused by buprenorphine and is accompanied by the proapoptotic ER stress response that involves the procaspase-3/CHOP pathway. Primary astrocyte cultures derived from the neonates of the buprenorphine group also displayed aberrant ER calcium mobilization and elevated basal levels of cyclooxygenase-2 (COX-2) at 14 days in vitro while showing sensitivity to lipopolysaccharide-activated expression of COX-2. Similarly, these long-lasting defects in the hippocampus and astrocytes were abolished by dextromethorphan. Our findings suggest that prenatal exposure to buprenorphine might instigate long-lasting effects on hippocampal and astrocytic functions. The beneficial effects of prenatal coadministration of dextromethorphan might be, at least in part, attributed to its properties in attenuating astrocyte activation and hippocampal ER stress in neonates.

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The Pharmacokinetics and Pharmacodynamics of Buprenorphine in Neonatal Abstinence Syndrome

Cited by 31 publications

References 27 publications

Buprenorphine in Neonatal Abstinence Syndrome

Buprenorphine in Neonatal Abstinence Syndrome

Opioid Treatment for Neonatal Opioid Withdrawal Syndrome: Current Challenges and Future Approaches

Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine

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