A pharmacokinetic-pharmacodynamic model of morphine exposure and subsequent morphine consumption in postoperative pain
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
A pharmacokinetic-pharmacodynamic model of morphine exposure and subsequent morphine consumption in postoperative pain. / Juul, Rasmus Vestergaard; Nyberg, Joakim; Lund, Trine Meldgaard; Rasmussen, Sten; Kreilgaard, Mads; Christrup, Lona Louring; Simonsson, Ulrika S H.
In: Pharmaceutical Research, Vol. 33, No. 5, 2016, p. 1093–1103.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - A pharmacokinetic-pharmacodynamic model of morphine exposure and subsequent morphine consumption in postoperative pain
AU - Juul, Rasmus Vestergaard
AU - Nyberg, Joakim
AU - Lund, Trine Meldgaard
AU - Rasmussen, Sten
AU - Kreilgaard, Mads
AU - Christrup, Lona Louring
AU - Simonsson, Ulrika S H
PY - 2016
Y1 - 2016
N2 - PurposeTo characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation.MethodsDose, formulation and time of morphine administration was available from a published study in 63 patients receiving intravenous, oral immediate release or oral controlled release morphine on request after hip surgery. The PK-PD relationship between predicted exposure of morphine and morphine consumption was modeled using repeated time to event (RTTE) modeling in NONMEM. To validate the RTTE model, a visual predictive check method was developed with simulated morphine consumption given the exposure of preceding morphine administration.ResultsThe probability of requesting morphine was found to be significantly related to the exposure of morphine as well as night/day. Oral controlled release morphine was more effective than intravenous and oral immediate release formulations at equivalent average concentrations. Maximum effect was obtained for 8 h by oral controlled release doses ≥ 15 mg, where probability of requesting a new dose was reduced to 20% for a typical patient.ConclusionThis study demonstrates the first quantitative link between exposure of morphine and subsequent morphine consumption and introduces an efficient visual predictive check approach with simulation of adaptive dosing.
AB - PurposeTo characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation.MethodsDose, formulation and time of morphine administration was available from a published study in 63 patients receiving intravenous, oral immediate release or oral controlled release morphine on request after hip surgery. The PK-PD relationship between predicted exposure of morphine and morphine consumption was modeled using repeated time to event (RTTE) modeling in NONMEM. To validate the RTTE model, a visual predictive check method was developed with simulated morphine consumption given the exposure of preceding morphine administration.ResultsThe probability of requesting morphine was found to be significantly related to the exposure of morphine as well as night/day. Oral controlled release morphine was more effective than intravenous and oral immediate release formulations at equivalent average concentrations. Maximum effect was obtained for 8 h by oral controlled release doses ≥ 15 mg, where probability of requesting a new dose was reduced to 20% for a typical patient.ConclusionThis study demonstrates the first quantitative link between exposure of morphine and subsequent morphine consumption and introduces an efficient visual predictive check approach with simulation of adaptive dosing.
U2 - 10.1007/s11095-015-1853-5
DO - 10.1007/s11095-015-1853-5
M3 - Tidsskriftartikel
VL - 33
SP - 1093
EP - 1103
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
IS - 5
ER -
ID: 152964519