Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers

Nasser, Azmi; Heidbreder, Christian; Liu, Yongzhen; Fudala, Paul J.

doi:10.1007/s40262-015-0238-6

Cited by 32 publications

(31 citation statements)

References 25 publications

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“…Hepatitis C virus–seropositive subjects have been shown to have higher buprenorphine exposure compared with seronegative subjects . In patients with moderate hepatic impairment, buprenorphine and naloxone exposures are increased up to 3‐fold, whereas in patients with more severe hepatic impairment, naloxone concentrations increase up to 10‐fold compared with healthy individuals . Therefore, treatment with buprenorphine is not recommended in patients with severe hepatic impairment and may be inappropriate for patients with moderate hepatic impairment …”

Section: Pathobiology Of Chronic Liver Diseasesmentioning

confidence: 99%

Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment

Talal

Venuto

Younis

2017

Clinical Pharm in Drug Dev

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While the liver is the primary site of metabolism and biliary excretion for many medications, data are limited on the liver’s pharmacokinetic abilities in cirrhosis. Cirrhosis develops through collagen deposition eventually culminating in end-stage liver disease that compromises hepatic drug metabolism. Consequently, the United States Food and Drug Administration (US FDA) recommends evaluating the pharmacokinetics of medications in subjects with hepatic impairment if hepatic metabolism constitutes more than 20% of their elimination or if they have a narrow therapeutic range. A variety of noninvasive indices and radiologic procedures can be employed to assess hepatic drug metabolism and excretion. The Child-Pugh score is the most commonly used scale for assessing hepatic impairment among drugs submitted for US FDA approval. The score, originally developed to guide operative mortality in patients undergoing hepatic resection, has not been modified since its inception five decades ago. Furthermore, the score was not originally intended to be a guide for potential dose modification in patients with hepatic impairment. These reasons, in combination with the availability of a variety of new imaging modalities and an enhanced understanding of hepatic biology, should foster the development of novel methods to assess the effect of hepatic impairment on liver drug metabolism.

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Section: Pathobiology Of Chronic Liver Diseasesmentioning

confidence: 99%

Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment

Talal

Venuto

Younis

2017

Clinical Pharm in Drug Dev

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“…Both buprenorphine and naloxone are extensively metabolized in the liver. To date, only 1 study, to our knowledge, has analyzed the pharmacokinetics of these 2 drugs in patients with impaired liver function . Nasser et al evaluated buprenorphine and naloxone pharmacokinetics in 33 subjects: 19 with impaired liver function according to the Child‐Pugh classification (ie, cirrhosis), 6 with chronic HCV infection and no liver impairment, and 8 healthy controls.…”

Section: Effect Of Impaired Liver Function On Drugs Used To Treat Submentioning

confidence: 99%

“…To date, only 1 study, to our knowledge, has analyzed the pharmacokinetics of these 2 drugs in patients with impaired liver function. 23 Nasser et al evaluated buprenorphine and naloxone pharmacokinetics in 33 subjects: 19 with impaired liver function according to the Child-Pugh classification (ie, cirrhosis), 6 with chronic HCV infection and no liver impairment, and 8 healthy controls. Although pharmacokinetic parameters did not change significantly in patients with compensated cirrhosis (Child-Pugh A) and noncirrhotic HCV patients, severe and moderate liver impairment (Child-Pugh B and C) significantly increased exposure to naloxone and, to a lesser extent, buprenorphine.…”

Section: Effect Of Impaired Liver Function On Drugs Used To Treat Submentioning

confidence: 99%

Liver Disease and Fibrosis Assessment in Substance Use–Related Disorders

Zeremski

Martinez

2017

Clinical Pharm in Drug Dev

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Substance users have the highest prevalence of hepatitis C virus (HCV) infection but have rarely been treated, largely because of their mistrust of the health care system, misconceptions about the consequences of the infection, and concerns regarding interferon-related side effects. With the development of highly efficacious, interferon-free therapeutic regimens without significant side effects, the concept of colocating HCV and substance use treatment would appear to be highly feasible. This process has been further facilitated by widespread clinical adaptation of noninvasive assays for fibrosis assessment, which could be performed routinely in substance use treatment facilities. The most commonly used noninvasive fibrosis assessment methods are serum marker indexes and transient elastography, both of which are very accurate in detecting cirrhosis or the absence of fibrosis, but much less successful in identifying intermediate fibrosis stages. The effect of drugs of abuse on the liver is not completely understood or sufficiently studied. There are no indications that heroin and cocaine affect fibrosis progression, but some recreational drugs (eg, alcohol and cannabis) can induce hepatic injury. In addition, knowledge gaps exist on the effect of impaired liver function on metabolism or transport of agents used to treat substance disorders as well as their interactions with HCV antivirals.

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“…BUP is metabolized by cytochrome P450 (CYP), mainly CYP3A4 and CYP2C8 in humans to form norbuprenorphine (NBUP) . NX is metabolized to nornaloxone by CYP2C18 and 2C19 . In addition, BUP, NBUP and NX undergo extensive glucuronidation by glucuronosyltransferases (UGT), UGT1A1, 1A3 and 2B7 .…”

Section: Introductionmentioning

confidence: 99%

Improving the oral bioavailability of buprenorphine: an in-vivo proof of concept

Joshi

Halquist

Konsoula

et al. 2017

Journal of Pharmacy and Pharmacology

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Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers

Cited by 32 publications

References 25 publications

Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment

Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment

Liver Disease and Fibrosis Assessment in Substance Use–Related Disorders

Improving the oral bioavailability of buprenorphine: an in-vivo proof of concept

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