Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Pharmacokinetic-pharmacodynamic modelling of the analgesic and antihyperalgesic effects of morphine after intravenous infusion in human volunteers

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Oral Immunosuppressive Treatment of Myasthenia Gravis in Denmark: A Nationwide Drug Utilization Study, 1996-2013

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A Systematic Review on Insulin Overdose Cases: Clinical Course, Complications and Novel Treatment Options

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. A national center for persistent severe pain after groin hernia repair: Five-year prospective data

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. A∂- and not C-Fibers Mediate Thermal Hyperalgesia to Short Laser Stimuli After Burn Injury in Man

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy individuals (15 males). The subjects were chosen based on a previous trial where 100 subjects rated (VAS) their pain during a heat injury (47°C, 7 min., 12.5 cm(2) ). The 33% lowest- and highest pain-sensitive subjects were offered participation in the present study. A two-compartment linear model with allometric scaling for weight provided the best description of the plasma concentration-time profile of morphine. Changes in the EPTo and 2HA responses with time during the placebo treatment were best described by a linear model and a quadratic model, respectively. The model discrimination process showed clear evidence for adding between-occasion variability (BOV) on baseline and the placebo slope for EPTo and 2HA, respectively. The sensitivity covariate was significant on baseline EPTo values and genetics as a covariate on the placebo slope for 2HA. The analgesic and antihyperalgesic effects of morphine were pharmacologically distinct as the models had different effect site equilibration half-lives and different covariate effects. Morphine had negligible effect on 2HA, but significant effect on EPTo.

OriginalsprogEngelsk
TidsskriftBasic & clinical pharmacology & toxicology
Vol/bind115
Udgave nummer3
Sider (fra-til)257-67
Antal sider11
ISSN1742-7843
DOI
StatusUdgivet - sep. 2014

ID: 44991313