A Pharmacologic Evaluation of Buprenorphine in Pregnancy and the Postpartum Period.

IF 4.2 3区 医学 Q1 SUBSTANCE ABUSE
Steve N Caritis, Raman Venkataramanan
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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.

丁丙诺啡在孕期和产后的药理评估。
背景:目的:比较孕期和产后血浆丁丙诺啡的药代动力学,并将丁丙诺啡浓度与瞳孔直径、临床阿片类药物戒断量表(COWS)和渴求评分等药效学终点联系起来:前瞻性队列:22 名孕妇在孕期或产后接受了 33 次药理学研究(每次 6-8 小时)。参与者每 6 或 8 小时服用一次 2-8 毫克舌下丁丙诺啡的稳定日剂量。给药频率由参与者自行选择。在研究当天,先测量血浆丁丙诺啡、瞳孔直径、COWS和渴求评分的基线值,然后在通常的早晨服药,并在一个服药间隔期内多次重复测量:研究结果:妊娠期血浆丁丙诺啡浓度时间曲线下的剂量标准化面积(155 ± 52 ng × min/mL)显著(P = 0.036)低于产后(218 ± 113 ng × min/mL)。无论给药频率如何,布丙诺啡在给药周期开始时(1.1 ± 0.7 纳克/毫升)和结束时(1.2 ± 0.8 纳克/毫升)的谷值浓度相似。当丁丙诺啡浓度接近 ~1 纳克/毫升时,瞳孔直径、COWS 和渴求评分恢复到基线:结论:孕妇需要更高的丁丙诺啡剂量才能达到与非孕妇相当的浓度。血浆丁丙诺啡浓度与瞳孔直径、COWS 和渴求评分等药效学指标之间存在时间关系。平均血浆浓度约为 1 纳克/毫升与 COWS 和渴求评分的最低水平相关。
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来源期刊
Journal of Addiction Medicine
Journal of Addiction Medicine 医学-药物滥用
CiteScore
6.10
自引率
9.10%
发文量
260
审稿时长
>12 weeks
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.
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