A Pharmacokinetic-Pharmacodynamic Model of Morphine Exposure and Subsequent Morphine Consumption in Postoperative Pain.
Pharm Res
; 33(5): 1093-103, 2016 May.
Article
em En
| MEDLINE
| ID: mdl-26753622
ABSTRACT
PURPOSE:
To characterize the pharmacokinetic-pharmacodynamic (PK-PD) relationship between exposure of morphine and subsequent morphine consumption and to develop simulation tools for model validation.METHODS:
Dose, 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.RESULTS:
The 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.CONCLUSION:
This 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dor Pós-Operatória
/
Analgésicos Opioides
/
Morfina
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article