Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats
The pharmacokinetic-pharmacodynamic (pk-pd) characterization of the in vivo antinociceptive interaction between (+)-O-desmethyltramadol [(+)-M1] and (-)-O-desmethyltramadol [(-)-M1], main metabolites of tramadol, was studied in three groups of rats. (+)-M1 and (-)-M1, both with different pd properti...
| Main Authors: | , , , , |
|---|---|
| Format: | info:eu-repo/semantics/article |
| Language: | eng |
| Published: |
Williams & Wilkins
2012
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/21763 |
| _version_ | 1793400196493737984 |
|---|---|
| author | Garrido, M.J. (María Jesús) Valle, M. (Marta) Campanero, M.A. (Miguel Angel) Calvo, R. (Rosario) Troconiz, I.F. (Iñaki F.) |
| author_facet | Garrido, M.J. (María Jesús) Valle, M. (Marta) Campanero, M.A. (Miguel Angel) Calvo, R. (Rosario) Troconiz, I.F. (Iñaki F.) |
| author_sort | Garrido, M.J. (María Jesús) |
| collection | DSpace |
| description | The pharmacokinetic-pharmacodynamic (pk-pd) characterization of the in vivo antinociceptive interaction between (+)-O-desmethyltramadol [(+)-M1] and (-)-O-desmethyltramadol [(-)-M1], main metabolites of tramadol, was studied in three groups of rats. (+)-M1 and (-)-M1, both with different pd properties, were studied under steady-state and nonsteady-state conditions, depending on the group. Plasma drug concentration and antinociception were simultaneously measured in each animal by using an enantioselective analytical assay and the tail-flick test, respectively. Respiratory depression also was evaluated in another series of experiments according to the same experimental conditions. The pk behavior was similar for both enantiomers and no significant (P >.05) interaction between two compounds was found at this level. However, a significant (P <.01) potentiation in the antinociceptive effect elicited by (+)-M1 was found during and after (-)-M1 administration. The pd model used to describe the time course of the antinociception in the presence of (+)-M1, (-)-M1, or both is based on previous knowledge of the compounds and includes the following: 1) an effect compartment model to account for the opioid effect of (+)-M1, and 2) an indirect response model accounting for the release of noradrenaline (NA) caused by (+)-M1, and the inhibition of the NA reuptake due to the action of (-)-M1. The model predicts a positive contribution to antinociception of the predicted increasing levels of NA. No significant (P >.05) respiratory effects were seen during or after (+)-M1 and (-)-M1 administration. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-21763 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2012 |
| publisher | Williams & Wilkins |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-217632021-05-24T13:19:18Z Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats Garrido, M.J. (María Jesús) Valle, M. (Marta) Campanero, M.A. (Miguel Angel) Calvo, R. (Rosario) Troconiz, I.F. (Iñaki F.) Antinociception Tramadol Pk-pd model Enantiomers The pharmacokinetic-pharmacodynamic (pk-pd) characterization of the in vivo antinociceptive interaction between (+)-O-desmethyltramadol [(+)-M1] and (-)-O-desmethyltramadol [(-)-M1], main metabolites of tramadol, was studied in three groups of rats. (+)-M1 and (-)-M1, both with different pd properties, were studied under steady-state and nonsteady-state conditions, depending on the group. Plasma drug concentration and antinociception were simultaneously measured in each animal by using an enantioselective analytical assay and the tail-flick test, respectively. Respiratory depression also was evaluated in another series of experiments according to the same experimental conditions. The pk behavior was similar for both enantiomers and no significant (P >.05) interaction between two compounds was found at this level. However, a significant (P <.01) potentiation in the antinociceptive effect elicited by (+)-M1 was found during and after (-)-M1 administration. The pd model used to describe the time course of the antinociception in the presence of (+)-M1, (-)-M1, or both is based on previous knowledge of the compounds and includes the following: 1) an effect compartment model to account for the opioid effect of (+)-M1, and 2) an indirect response model accounting for the release of noradrenaline (NA) caused by (+)-M1, and the inhibition of the NA reuptake due to the action of (-)-M1. The model predicts a positive contribution to antinociception of the predicted increasing levels of NA. No significant (P >.05) respiratory effects were seen during or after (+)-M1 and (-)-M1 administration. 2012-04-24T07:55:50Z 2012-04-24T07:55:50Z 2000 info:eu-repo/semantics/article https://hdl.handle.net/10171/21763 eng info:eu-repo/semantics/openAccess application/pdf Williams & Wilkins |
| spellingShingle | Antinociception Tramadol Pk-pd model Enantiomers Garrido, M.J. (María Jesús) Valle, M. (Marta) Campanero, M.A. (Miguel Angel) Calvo, R. (Rosario) Troconiz, I.F. (Iñaki F.) Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats |
| title | Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats |
| title_full | Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats |
| title_fullStr | Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats |
| title_full_unstemmed | Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats |
| title_short | Modeling of the In Vivo Antinociceptive Interaction between an Opioid Agonist, (+)-O-Desmethyltramadol, and a Monoamine Reuptake Inhibitor, (—)-O-Desmethyltramadol, in Rats |
| title_sort | modeling of the in vivo antinociceptive interaction between an opioid agonist, (+)-o-desmethyltramadol, and a monoamine reuptake inhibitor, (—)-o-desmethyltramadol, in rats |
| topic | Antinociception Tramadol Pk-pd model Enantiomers |
| url | https://hdl.handle.net/10171/21763 |
| work_keys_str_mv | AT garridomjmariajesus modelingoftheinvivoantinociceptiveinteractionbetweenanopioidagonistodesmethyltramadolandamonoaminereuptakeinhibitorodesmethyltramadolinrats AT vallemmarta modelingoftheinvivoantinociceptiveinteractionbetweenanopioidagonistodesmethyltramadolandamonoaminereuptakeinhibitorodesmethyltramadolinrats AT campaneromamiguelangel modelingoftheinvivoantinociceptiveinteractionbetweenanopioidagonistodesmethyltramadolandamonoaminereuptakeinhibitorodesmethyltramadolinrats AT calvorrosario modelingoftheinvivoantinociceptiveinteractionbetweenanopioidagonistodesmethyltramadolandamonoaminereuptakeinhibitorodesmethyltramadolinrats AT troconizifinakif modelingoftheinvivoantinociceptiveinteractionbetweenanopioidagonistodesmethyltramadolandamonoaminereuptakeinhibitorodesmethyltramadolinrats |