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Asbjørn Mohr Drewes

Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. / Staahl, Camilla; Upton, Richard; Foster, David J R; Christrup, Lona Louring; Kristensen, Kim; Hansen, Steen Honoré; Arendt-Nielsen, Lars; Drewes, Asbjørn Mohr.

I: The Journal of Clinical Pharmacology, Bind 48, Nr. 5, 2008, s. 619-31.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Staahl, C, Upton, R, Foster, DJR, Christrup, LL, Kristensen, K, Hansen, SH, Arendt-Nielsen, L & Drewes, AM 2008, 'Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model', The Journal of Clinical Pharmacology, bind 48, nr. 5, s. 619-31. https://doi.org/10.1177/0091270008314465

APA

Staahl, C., Upton, R., Foster, D. J. R., Christrup, L. L., Kristensen, K., Hansen, S. H., Arendt-Nielsen, L., & Drewes, A. M. (2008). Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. The Journal of Clinical Pharmacology, 48(5), 619-31. https://doi.org/10.1177/0091270008314465

CBE

Staahl C, Upton R, Foster DJR, Christrup LL, Kristensen K, Hansen SH, Arendt-Nielsen L, Drewes AM. 2008. Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. The Journal of Clinical Pharmacology. 48(5):619-31. https://doi.org/10.1177/0091270008314465

MLA

Vancouver

Staahl C, Upton R, Foster DJR, Christrup LL, Kristensen K, Hansen SH o.a. Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. The Journal of Clinical Pharmacology. 2008;48(5):619-31. https://doi.org/10.1177/0091270008314465

Author

Staahl, Camilla ; Upton, Richard ; Foster, David J R ; Christrup, Lona Louring ; Kristensen, Kim ; Hansen, Steen Honoré ; Arendt-Nielsen, Lars ; Drewes, Asbjørn Mohr. / Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model. I: The Journal of Clinical Pharmacology. 2008 ; Bind 48, Nr. 5. s. 619-31.

Bibtex

@article{db987ac0e86f11dd8f9a000ea68e967b,
title = "Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model",
abstract = "Analgesia from most opioids is mediated by mu receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia. Twenty-four healthy subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal, and electrical pain tests were performed in the skin and viscera. Blood samples and pain measurements were taken at baseline and after 15, 30, 60, 90, and 120 minutes. Pharmacokinetic/pharmacodynamic profiles were modeled using a 2-stage, nonlinear, mixed-effects approach with an effect compartment to represent the concentration-analgesia delay. Morphine kinetics was best described by a 2-compartment model, whereas oxycodone kinetics was best described with a 1-compartment model. Generally the analgesic effects of morphine were best related to plasma concentration by introducing a delay via an effect compartment. However, for oxycodone, this was only the case for analgesia in the somatic pain measures, whereas the plasma concentration correlated better to the course of the analgesia with no delay in the visceral pain measures. Oxycodone and morphine showed different pharmacodynamic/pharmacokinetic relationships for the visceral analgesia, whereas relationships were alike for somatic analgesia.",
keywords = "Administration, Oral, Adult, Algorithms, Analgesics, Opioid, Area Under Curve, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Electric Stimulation, Female, Hot Temperature, Humans, Infusions, Parenteral, Male, Models, Biological, Morphine, Oxycodone, Pain, Pain Measurement, Pain Threshold, Physical Stimulation",
author = "Camilla Staahl and Richard Upton and Foster, {David J R} and Christrup, {Lona Louring} and Kim Kristensen and Hansen, {Steen Honor{\'e}} and Lars Arendt-Nielsen and Drewes, {Asbj{\o}rn Mohr}",
year = "2008",
doi = "10.1177/0091270008314465",
language = "English",
volume = "48",
pages = "619--31",
journal = "The Journal of Clinical Pharmacology",
issn = "0091-2700",
publisher = "Sage Science Press (US)",
number = "5",

}

RIS

TY - JOUR

T1 - Pharmacokinetic-pharmacodynamic modeling of morphine and oxycodone concentrations and analgesic effect in a multimodal experimental pain model

AU - Staahl, Camilla

AU - Upton, Richard

AU - Foster, David J R

AU - Christrup, Lona Louring

AU - Kristensen, Kim

AU - Hansen, Steen Honoré

AU - Arendt-Nielsen, Lars

AU - Drewes, Asbjørn Mohr

PY - 2008

Y1 - 2008

N2 - Analgesia from most opioids is mediated by mu receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia. Twenty-four healthy subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal, and electrical pain tests were performed in the skin and viscera. Blood samples and pain measurements were taken at baseline and after 15, 30, 60, 90, and 120 minutes. Pharmacokinetic/pharmacodynamic profiles were modeled using a 2-stage, nonlinear, mixed-effects approach with an effect compartment to represent the concentration-analgesia delay. Morphine kinetics was best described by a 2-compartment model, whereas oxycodone kinetics was best described with a 1-compartment model. Generally the analgesic effects of morphine were best related to plasma concentration by introducing a delay via an effect compartment. However, for oxycodone, this was only the case for analgesia in the somatic pain measures, whereas the plasma concentration correlated better to the course of the analgesia with no delay in the visceral pain measures. Oxycodone and morphine showed different pharmacodynamic/pharmacokinetic relationships for the visceral analgesia, whereas relationships were alike for somatic analgesia.

AB - Analgesia from most opioids is mediated by mu receptors located mainly in the central nervous system. Previous studies have shown a different pharmacological profile of oxycodone in respect to visceral analgesia. This study investigated if morphine and oxycodone have different pharmacokinetic/pharmacodynamic profiles, in particular with respect to delay between opioid blood concentration and analgesia. Twenty-four healthy subjects had oral morphine (30 mg), oxycodone (15 mg), or placebo. Mechanical, thermal, and electrical pain tests were performed in the skin and viscera. Blood samples and pain measurements were taken at baseline and after 15, 30, 60, 90, and 120 minutes. Pharmacokinetic/pharmacodynamic profiles were modeled using a 2-stage, nonlinear, mixed-effects approach with an effect compartment to represent the concentration-analgesia delay. Morphine kinetics was best described by a 2-compartment model, whereas oxycodone kinetics was best described with a 1-compartment model. Generally the analgesic effects of morphine were best related to plasma concentration by introducing a delay via an effect compartment. However, for oxycodone, this was only the case for analgesia in the somatic pain measures, whereas the plasma concentration correlated better to the course of the analgesia with no delay in the visceral pain measures. Oxycodone and morphine showed different pharmacodynamic/pharmacokinetic relationships for the visceral analgesia, whereas relationships were alike for somatic analgesia.

KW - Administration, Oral

KW - Adult

KW - Algorithms

KW - Analgesics, Opioid

KW - Area Under Curve

KW - Cross-Over Studies

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Electric Stimulation

KW - Female

KW - Hot Temperature

KW - Humans

KW - Infusions, Parenteral

KW - Male

KW - Models, Biological

KW - Morphine

KW - Oxycodone

KW - Pain

KW - Pain Measurement

KW - Pain Threshold

KW - Physical Stimulation

U2 - 10.1177/0091270008314465

DO - 10.1177/0091270008314465

M3 - Journal article

C2 - 18440921

VL - 48

SP - 619

EP - 631

JO - The Journal of Clinical Pharmacology

JF - The Journal of Clinical Pharmacology

SN - 0091-2700

IS - 5

ER -