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- Publisher Website: 10.1002/CPT.66
- Scopus: eid_2-s2.0-84929138347
- PMID: 25669174
- WOS: WOS:000351432700028
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Article: Altered Morphine Glucuronide and Bile Acid Disposition in Patients With Nonalcoholic Steatohepatitis
Title | Altered Morphine Glucuronide and Bile Acid Disposition in Patients With Nonalcoholic Steatohepatitis |
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Authors | |
Issue Date | 2015 |
Citation | Clinical Pharmacology and Therapeutics, 2015, v. 97, n. 4, p. 419-427 How to Cite? |
Abstract | The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically derived morphine glucuronide (morphine-3-and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (Cmax) and area under the concentration-time curve (AUC0-last) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225 nM and 58.8 vs. 37.2 mM*min, respectively; P ≤ 0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide Cmax and AUC0-last (P < 0.001). Fasting serum glycocholate, taurocholate, and total bile acid concentrations were associated with NASH severity (P < 0.006). Increased hepatic basolateral efflux of morphine glucuronide and bile acids is consistent with altered hepatic transport protein expression in patients with NASH and may partially explain differences in efficacy and/or toxicity of some highly transported anionic drugs/metabolites in this patient population. |
Persistent Identifier | http://hdl.handle.net/10722/342488 |
ISSN | 2023 Impact Factor: 6.3 2023 SCImago Journal Rankings: 1.988 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Ferslew, B. C. | - |
dc.contributor.author | Johnston, C. K. | - |
dc.contributor.author | Tsakalozou, E. | - |
dc.contributor.author | Bridges, A. S. | - |
dc.contributor.author | Paine, M. F. | - |
dc.contributor.author | Jia, W. | - |
dc.contributor.author | Stewart, P. W. | - |
dc.contributor.author | Barritt, A. S. | - |
dc.contributor.author | Brouwer, K. L.R. | - |
dc.date.accessioned | 2024-04-17T07:04:10Z | - |
dc.date.available | 2024-04-17T07:04:10Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Clinical Pharmacology and Therapeutics, 2015, v. 97, n. 4, p. 419-427 | - |
dc.identifier.issn | 0009-9236 | - |
dc.identifier.uri | http://hdl.handle.net/10722/342488 | - |
dc.description.abstract | The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically derived morphine glucuronide (morphine-3-and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (Cmax) and area under the concentration-time curve (AUC0-last) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225 nM and 58.8 vs. 37.2 mM*min, respectively; P ≤ 0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide Cmax and AUC0-last (P < 0.001). Fasting serum glycocholate, taurocholate, and total bile acid concentrations were associated with NASH severity (P < 0.006). Increased hepatic basolateral efflux of morphine glucuronide and bile acids is consistent with altered hepatic transport protein expression in patients with NASH and may partially explain differences in efficacy and/or toxicity of some highly transported anionic drugs/metabolites in this patient population. | - |
dc.language | eng | - |
dc.relation.ispartof | Clinical Pharmacology and Therapeutics | - |
dc.title | Altered Morphine Glucuronide and Bile Acid Disposition in Patients With Nonalcoholic Steatohepatitis | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1002/CPT.66 | - |
dc.identifier.pmid | 25669174 | - |
dc.identifier.scopus | eid_2-s2.0-84929138347 | - |
dc.identifier.volume | 97 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 419 | - |
dc.identifier.epage | 427 | - |
dc.identifier.eissn | 1532-6535 | - |
dc.identifier.isi | WOS:000351432700028 | - |