Interaction of ethanol with codeine metabolism in rat hepatocytes: a multicompartmental model

E. Bodd, M. H. Green, Ca Drevon, J. Mørland

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A multicompartmental pharmacokinetic model is presented, which based upon data from a previous study, describes the effects of ethanol (60 m M) on the metabolism of codeine (10 μM) in isolated rat hepatocytes. According to this model, about one third of codeine metabolized was transformed to morphine (13%) and norcodeine (18%), and two-thirds to unknown metabolites in the absence of ethanol. In the presence of ethanol, the apparent first order fractional rate of total codeine metabolism was reduced by 66% (0.0783 vs 0.0271 min-1). There was no alteration in the portion of codeine metabolized to norcodeine, but there was a 44% decrease in the fraction transformed to unknown metabolites and a tripling in the portion transformed to morphine. The fractional rate of codeine O-demethylation to morphine was apparently not sensitive to ethanol. In the absence of ethanol, about two-thirds of morphine was metabolized to morphine-3-glucuronide and the other third to unidentified metabolites. Only the glucuronidation process seemed to be inhibited by ethanol. The fractional rate of further metabolism of norcodeine to normorphine was similar in the absence or presence of ethanol. In conclusion ethanol co-incubation with codeine resulted in an inhibition of codeine conversion to unknown metabolites and norcodeine, and with morphine to morphine-3-glucuronide, but no inhibition in morphine production.

Original languageEnglish (US)
Pages (from-to)239-243
Number of pages5
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume11
Issue number3
DOIs
StatePublished - Jul 1 1986

Fingerprint

Codeine
Hepatocytes
Ethanol
Morphine
Pharmacokinetics
norcodeine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{47f73e1a03064de1b9e4cc0bd0892ae4,
title = "Interaction of ethanol with codeine metabolism in rat hepatocytes: a multicompartmental model",
abstract = "A multicompartmental pharmacokinetic model is presented, which based upon data from a previous study, describes the effects of ethanol (60 m M) on the metabolism of codeine (10 μM) in isolated rat hepatocytes. According to this model, about one third of codeine metabolized was transformed to morphine (13{\%}) and norcodeine (18{\%}), and two-thirds to unknown metabolites in the absence of ethanol. In the presence of ethanol, the apparent first order fractional rate of total codeine metabolism was reduced by 66{\%} (0.0783 vs 0.0271 min-1). There was no alteration in the portion of codeine metabolized to norcodeine, but there was a 44{\%} decrease in the fraction transformed to unknown metabolites and a tripling in the portion transformed to morphine. The fractional rate of codeine O-demethylation to morphine was apparently not sensitive to ethanol. In the absence of ethanol, about two-thirds of morphine was metabolized to morphine-3-glucuronide and the other third to unidentified metabolites. Only the glucuronidation process seemed to be inhibited by ethanol. The fractional rate of further metabolism of norcodeine to normorphine was similar in the absence or presence of ethanol. In conclusion ethanol co-incubation with codeine resulted in an inhibition of codeine conversion to unknown metabolites and norcodeine, and with morphine to morphine-3-glucuronide, but no inhibition in morphine production.",
author = "E. Bodd and Green, {M. H.} and Ca Drevon and J. M{\o}rland",
year = "1986",
month = "7",
day = "1",
doi = "10.1007/BF03189852",
language = "English (US)",
volume = "11",
pages = "239--243",
journal = "European Journal of Drug Metabolism and Pharmacokinetics",
issn = "0378-7966",
publisher = "Springer Paris",
number = "3",

}

Interaction of ethanol with codeine metabolism in rat hepatocytes : a multicompartmental model. / Bodd, E.; Green, M. H.; Drevon, Ca; Mørland, J.

In: European Journal of Drug Metabolism and Pharmacokinetics, Vol. 11, No. 3, 01.07.1986, p. 239-243.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interaction of ethanol with codeine metabolism in rat hepatocytes

T2 - a multicompartmental model

AU - Bodd, E.

AU - Green, M. H.

AU - Drevon, Ca

AU - Mørland, J.

PY - 1986/7/1

Y1 - 1986/7/1

N2 - A multicompartmental pharmacokinetic model is presented, which based upon data from a previous study, describes the effects of ethanol (60 m M) on the metabolism of codeine (10 μM) in isolated rat hepatocytes. According to this model, about one third of codeine metabolized was transformed to morphine (13%) and norcodeine (18%), and two-thirds to unknown metabolites in the absence of ethanol. In the presence of ethanol, the apparent first order fractional rate of total codeine metabolism was reduced by 66% (0.0783 vs 0.0271 min-1). There was no alteration in the portion of codeine metabolized to norcodeine, but there was a 44% decrease in the fraction transformed to unknown metabolites and a tripling in the portion transformed to morphine. The fractional rate of codeine O-demethylation to morphine was apparently not sensitive to ethanol. In the absence of ethanol, about two-thirds of morphine was metabolized to morphine-3-glucuronide and the other third to unidentified metabolites. Only the glucuronidation process seemed to be inhibited by ethanol. The fractional rate of further metabolism of norcodeine to normorphine was similar in the absence or presence of ethanol. In conclusion ethanol co-incubation with codeine resulted in an inhibition of codeine conversion to unknown metabolites and norcodeine, and with morphine to morphine-3-glucuronide, but no inhibition in morphine production.

AB - A multicompartmental pharmacokinetic model is presented, which based upon data from a previous study, describes the effects of ethanol (60 m M) on the metabolism of codeine (10 μM) in isolated rat hepatocytes. According to this model, about one third of codeine metabolized was transformed to morphine (13%) and norcodeine (18%), and two-thirds to unknown metabolites in the absence of ethanol. In the presence of ethanol, the apparent first order fractional rate of total codeine metabolism was reduced by 66% (0.0783 vs 0.0271 min-1). There was no alteration in the portion of codeine metabolized to norcodeine, but there was a 44% decrease in the fraction transformed to unknown metabolites and a tripling in the portion transformed to morphine. The fractional rate of codeine O-demethylation to morphine was apparently not sensitive to ethanol. In the absence of ethanol, about two-thirds of morphine was metabolized to morphine-3-glucuronide and the other third to unidentified metabolites. Only the glucuronidation process seemed to be inhibited by ethanol. The fractional rate of further metabolism of norcodeine to normorphine was similar in the absence or presence of ethanol. In conclusion ethanol co-incubation with codeine resulted in an inhibition of codeine conversion to unknown metabolites and norcodeine, and with morphine to morphine-3-glucuronide, but no inhibition in morphine production.

UR - http://www.scopus.com/inward/record.url?scp=0022968523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022968523&partnerID=8YFLogxK

U2 - 10.1007/BF03189852

DO - 10.1007/BF03189852

M3 - Article

C2 - 3816880

AN - SCOPUS:0022968523

VL - 11

SP - 239

EP - 243

JO - European Journal of Drug Metabolism and Pharmacokinetics

JF - European Journal of Drug Metabolism and Pharmacokinetics

SN - 0378-7966

IS - 3

ER -