Advantage nonmem prediction full#
Advantage nonmem prediction software#

In this study we aimed to derive a population PK-PD model for propofol in adolescents undergoing idiopathic scoliosis surgery using two different PD endpoints. Moreover, whereas in adults different PD endpoints have been used in PKPD models, in children only Bispectral Index (BIS) and Comfort scores have been used to describe the time course of propofol effects in relation to the dose. However, even though adolescents are known to differ from both children and adults because of physiologic changes due to unique hormonal profiles and changes in body size and composition, only one PKPD model in (obese) adolescents was reported. To date, also a limited number of PKPD models in children have been published on the propofol dose-response relationship in children undergoing different types of surgery, and on the depth of sedation in non-ventilated children in the ICU. For adults, population models are available describing propofol PK PD during various types of surgery, different co-morbidities, and for patients admitted to the ICU.

While propofol pharmacokinetics (PK) are widely studied, there is a relative paucity of pharmacodynamic data. Propofol is frequently used for induction and maintenance of anesthesia in adults and children, as it has desirable pharmacokinetic and pharmacodynamic properties. This may imply that BIS and cAAI measure fundamentally different endpoints in the brain. Large differences were demonstrated between both monitors.

ConclusionsДЄ population PKPD model for propofol in adolescents was developed that successfully described the time course of propofol concentration, BIS and cAAI in individuals upon undergoing scoliosis surgery with intraoperative wake-up test and reinduction of anesthesia. The delay in PD effect in relation to plasma concentration was best described by a two compartment effect-site model with a ke o of 0.102вЂ‰min в€’вЂ‰1, ke 12 of 0.121вЂ‰min в€’вЂ‰1 and ke 21 of 0.172вЂ‰min в€’вЂ‰1. For the sigmoidal Emax model, the propofol concentration at half maximum effect (EC 50) was 3.51 and 2.14вЂ‰mg/L and Hill coefficient 1.43 and 6.85 for BIS and cAAI, respectively. The time courses of propofol concentrations, BIS and cAAI values during anesthesia, intra-operative wakeup and reduction of anesthesia were best described by a two-compartment PK model linked to an inhibitory sigmoidal Emax PD model. A propofol PKPD model was developed using NONMEM. BIS and cAAI were continuously measured and blood samples collected. MethodsДЇourteen adolescents (9.8вЂ“20.1вЂ‰years) were evaluated during standardized propofol-remifentanil anesthesia for idiopathic scoliosis surgery with an intraoperative wake-up test with reinduction of anesthesia. In this study we derived a PK-PD model for propofol in adolescents undergoing idiopathic scoliosis surgery with an intraoperative wake-up test with reinduction of anesthesia using both Bispectral Index (BIS) and composite A-line ARX index (cAAI) as endpoints. Model estimation and data simulation were performed using NONMEM version 5.1.In adolescents limited data are available on the pharmacokinetics (PK) and pharmacodynamics (PD) of propofol. We illustrate the use of the package with two simulated datasets, one under the true model and one with different parameter values, to show how npde can be used to evaluate models.

Advantage nonmem prediction software#

Simulations need to be performed before hand, using for example the software used for model estimation. Under the null hypothesis that the model under scrutiny describes the validation dataset, npde should follow the standard normal distribution.

Advantage nonmem prediction full#

npde take into account the full predictive distribution of each individual observation and handle multiple observations within subjects. In this paper, we describe an add-on package for the open source statistical package R, designed to compute npde. Recently, normalised prediction distribution errors (npde) have been proposed as a model evaluation tool.

Pharmacokinetic/pharmacodynamic data are often analysed using nonlinear mixed-effect models, and model evaluation should be an important part of the analysis.