{"title":"A Pharmacologic Evaluation of Buprenorphine in Pregnancy and the Postpartum Period.","authors":"Steve N Caritis, Raman Venkataramanan","doi":"10.1097/ADM.0000000000001380","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy.</p><p><strong>Aims: </strong>To compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores.</p><p><strong>Study design: </strong>Prospective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6-8 hours each) during pregnancy or postpartum. Participants were on a stable daily dose of 2-8 mg sublingual buprenorphine every 6 or 8 hours. The dosing frequency was selected by the participant. On study day, baseline measurements of plasma buprenorphine, pupil diameter, COWS, and craving scores were obtained, then the usual morning dose was taken, and measurements were repeated several times over 1 dosing interval.</p><p><strong>Findings: </strong>The dose-normalized area under the plasma buprenorphine concentration time curve was significantly (P = 0.036) lower during pregnancy (155 ± 52 ng × min/mL) than postpartum (218 ± 113 ng × min/mL). Buprenorphine trough concentrations were similar at the start (1.1 ± 0.7 ng/mL) and end of a dosing cycle (1.2 ± 0.8 ng/mL) regardless of dosing frequency. Pupillary diameter, COWS, and craving scores returned to baseline as buprenorphine concentrations approached ~1 ng/mL.</p><p><strong>Conclusions: </strong>Pregnant people require a higher dose of buprenorphine to achieve concentrations comparable to nonpregnant people. There is a temporal relationship between the plasma buprenorphine concentration and the pharmacodynamic markers of pupillary diameter, COWS, and craving scores. An average plasma concentration of ~1 ng/mL was associated with the lowest level of COWS and craving scores.</p>","PeriodicalId":14744,"journal":{"name":"Journal of Addiction Medicine","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Addiction Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/ADM.0000000000001380","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"SUBSTANCE ABUSE","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy.
Aims: To compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores.
Study design: Prospective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6-8 hours each) during pregnancy or postpartum. Participants were on a stable daily dose of 2-8 mg sublingual buprenorphine every 6 or 8 hours. The dosing frequency was selected by the participant. On study day, baseline measurements of plasma buprenorphine, pupil diameter, COWS, and craving scores were obtained, then the usual morning dose was taken, and measurements were repeated several times over 1 dosing interval.
Findings: The dose-normalized area under the plasma buprenorphine concentration time curve was significantly (P = 0.036) lower during pregnancy (155 ± 52 ng × min/mL) than postpartum (218 ± 113 ng × min/mL). Buprenorphine trough concentrations were similar at the start (1.1 ± 0.7 ng/mL) and end of a dosing cycle (1.2 ± 0.8 ng/mL) regardless of dosing frequency. Pupillary diameter, COWS, and craving scores returned to baseline as buprenorphine concentrations approached ~1 ng/mL.
Conclusions: Pregnant people require a higher dose of buprenorphine to achieve concentrations comparable to nonpregnant people. There is a temporal relationship between the plasma buprenorphine concentration and the pharmacodynamic markers of pupillary diameter, COWS, and craving scores. An average plasma concentration of ~1 ng/mL was associated with the lowest level of COWS and craving scores.
期刊介绍:
The mission of Journal of Addiction Medicine, the official peer-reviewed journal of the American Society of Addiction Medicine, is to promote excellence in the practice of addiction medicine and in clinical research as well as to support Addiction Medicine as a mainstream medical sub-specialty.
Under the guidance of an esteemed Editorial Board, peer-reviewed articles published in the Journal focus on developments in addiction medicine as well as on treatment innovations and ethical, economic, forensic, and social topics including:
•addiction and substance use in pregnancy
•adolescent addiction and at-risk use
•the drug-exposed neonate
•pharmacology
•all psychoactive substances relevant to addiction, including alcohol, nicotine, caffeine, marijuana, opioids, stimulants and other prescription and illicit substances
•diagnosis
•neuroimaging techniques
•treatment of special populations
•treatment, early intervention and prevention of alcohol and drug use disorders
•methodological issues in addiction research
•pain and addiction, prescription drug use disorder
•co-occurring addiction, medical and psychiatric disorders
•pathological gambling disorder, sexual and other behavioral addictions
•pathophysiology of addiction
•behavioral and pharmacological treatments
•issues in graduate medical education
•recovery
•health services delivery
•ethical, legal and liability issues in addiction medicine practice
•drug testing
•self- and mutual-help.