Effects of naloxegol on whole gut transit in opioid-naïve healthy subjects receiving codeine: A randomized, controlled trial

H. Halawi, P. Vijayvargiya, I. Busciglio, I. Oduyebo, D. Khemani, M. Ryks, D. Rhoten, D. Burton, Lawrence Szarka, Andres Acosta, Michael Camilleri

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. Aim: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. Methods: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2, colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2. Key Results: Participants were 59.7% women, median BMI 25.0 kg/m2, and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2. There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min [IQR 110.5-238.6]) and naloxegol (95.5 min [89.1-135.4]). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0% [0.0-45.0]) and naloxegol (51% [18.8-76.2]). However, no significant differences were found between codeine-treated participants concomitantly receiving placebo or naloxegol. Conclusions and Inferences: Short-term administration of naloxegol (25 mg) in healthy, opioid-naïve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid-naïve subjects.

Original languageEnglish (US)
JournalNeurogastroenterology and Motility
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Codeine
Opioid Analgesics
Healthy Volunteers
Randomized Controlled Trials
Gastric Emptying
Ascending Colon
Placebos
naloxegol
Narcotic Antagonists
mu Opioid Receptor
Opioid Receptors
Constipation
Nausea
Vomiting
Volunteers
Stomach

Keywords

  • Codeine
  • Constipation
  • Gastroparesis
  • Opioid
  • PAMORA

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

Effects of naloxegol on whole gut transit in opioid-naïve healthy subjects receiving codeine : A randomized, controlled trial. / Halawi, H.; Vijayvargiya, P.; Busciglio, I.; Oduyebo, I.; Khemani, D.; Ryks, M.; Rhoten, D.; Burton, D.; Szarka, Lawrence; Acosta, Andres; Camilleri, Michael.

In: Neurogastroenterology and Motility, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Effects of naloxegol on whole gut transit in opioid-na{\"i}ve healthy subjects receiving codeine: A randomized, controlled trial",
abstract = "Background: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. Aim: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. Methods: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-na{\"i}ve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2, colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2. Key Results: Participants were 59.7{\%} women, median BMI 25.0 kg/m2, and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2. There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min [IQR 110.5-238.6]) and naloxegol (95.5 min [89.1-135.4]). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0{\%} [0.0-45.0]) and naloxegol (51{\%} [18.8-76.2]). However, no significant differences were found between codeine-treated participants concomitantly receiving placebo or naloxegol. Conclusions and Inferences: Short-term administration of naloxegol (25 mg) in healthy, opioid-na{\"i}ve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid-na{\"i}ve subjects.",
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T1 - Effects of naloxegol on whole gut transit in opioid-naïve healthy subjects receiving codeine

T2 - A randomized, controlled trial

AU - Halawi, H.

AU - Vijayvargiya, P.

AU - Busciglio, I.

AU - Oduyebo, I.

AU - Khemani, D.

AU - Ryks, M.

AU - Rhoten, D.

AU - Burton, D.

AU - Szarka, Lawrence

AU - Acosta, Andres

AU - Camilleri, Michael

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. Aim: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. Methods: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2, colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2. Key Results: Participants were 59.7% women, median BMI 25.0 kg/m2, and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2. There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min [IQR 110.5-238.6]) and naloxegol (95.5 min [89.1-135.4]). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0% [0.0-45.0]) and naloxegol (51% [18.8-76.2]). However, no significant differences were found between codeine-treated participants concomitantly receiving placebo or naloxegol. Conclusions and Inferences: Short-term administration of naloxegol (25 mg) in healthy, opioid-naïve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid-naïve subjects.

AB - Background: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. Aim: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. Methods: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2, colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2. Key Results: Participants were 59.7% women, median BMI 25.0 kg/m2, and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2. There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min [IQR 110.5-238.6]) and naloxegol (95.5 min [89.1-135.4]). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0% [0.0-45.0]) and naloxegol (51% [18.8-76.2]). However, no significant differences were found between codeine-treated participants concomitantly receiving placebo or naloxegol. Conclusions and Inferences: Short-term administration of naloxegol (25 mg) in healthy, opioid-naïve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid-naïve subjects.

KW - Codeine

KW - Constipation

KW - Gastroparesis

KW - Opioid

KW - PAMORA

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