Intravenous Drug Delivery Systems Flashcards
(18 cards)
The delay between the plasma and the effect compartment is mathematically described by a single parameter, defined as …
ke0, the effect-site equilibration rate constant
If a constant plasma concentration is maintained, then the time required for the biophase concentration to reach 50% of the plasma concentration (the …) can be calculated as …
t1/2ke0
0.693/ke0
Time to Peak Drug Effect of alfentanil, fentanil, remifentanil, morphine, propofol and midazolam
alfentanil: 1,4 min
fentanil: 3,6 min
remifentanil: 1,8 min
morphine: 19 min
propofol: 1,6 min
midazolam: 2,8 min
The difference between the measured and target concentrations can be expressed in several ways.
Numerically, the primary concern is how far the measured concentration is from the predicted by the TCI model; this relationship is now most frequently described in terms of …, which is the difference between …
performance error
the measured and the target concentrations as a percentage of the desired target – for example, [(measured − target) ÷ target × 100%].
Describe the MDPE
The median value of the performance error for a patient or population is referred to as the median performance error (MDPE) and represents the average overshoot or undershoot of the system
Describe the MDAPE
The median absolute performance error (MDAPE) is the median of the absolute values of all performance errors. The MDAPE is commonly used as a measure of the inaccuracy of an automated drug delivery device. An MDAPE of zero is perfect performance, and an MDAPE of 20% means that one-half the plasma concentrations will be within 20% of the target and one half will be outside that range
Varvel and colleagues asked a group of clinicians to evaluate the performance of automated drug delivery devices and demonstrated that the … best predicted the adequacy of performance of the automated delivery device, as judged by
experienced clinicians.
MDAPE
What a does positive MDPE indicate? And a negative one?
The MDPE does not indicate the range of performance errors (because positive and negative performance errors offset each other), but it does indicate whether the plasma concentrations achieved with the device tend to overshoot (+MDPE) or undershoot (−MDPE) the desired target.
Based on many studies, the expected predictive performance of pharmacokinetic models, at best, tends to be around … MDAPE
20% to 30%
Coetzee and co-workers compared the accuracy of some of the models published before 1995 and found that propofol TCI using the model published by Marsh and co-workers resulted in acceptable performance (MDPE …%; MDAPE …%)
−7
18
The major drawback of the Marsh model is … and …
the lack of effect compartment information
the fact that weight is the only covariate
Schnider and co-workers evaluated … as covariates in a new combined pharmacokinetic–dynamic three-compartment model. The large variability of the study population (age … years, weight … kg) provides a wide applicability of the model. Several validation studies rated this model accurate under various conditions
age, height, weight, and lean body mass
18 to 81
44 to 123
Eleveld and colleagues combined data from 30 studies (15,433 propofol concentration measurements), of which 5 had simultaneous bispectral index registrations (28,639 BIS datapoints), derived from 1033 individual patients or
volunteers. With an age range between … years and a weight range between …, the Eleveld model is expected to be applicable in a broad population of patients
27 weeks postmenstrual age (PMA) up to 88
680g up to 160kg
The Eleveld structural model is a three-compartmental mammillary model in which classical demographic variables, such as … were identified as covariates. The James equation for lean body mass calculation (used in the … model for propofol and the … model for remifentanil) has been replaced by …, calculated using the … formula, which is more widely applicable and produces more realistic predictions in the … patient
age, weight, height, and sex,
Schnider
Minto
fat free mass (FFM)
Al-Sallami
morbidly obese
Pediatric Propofol Models
- Kataria and colleagues described the time course of propofol plasma concentration in a population of children between the ages of 3 and 11 years using a three-compartment model with weight as the
sole significant covariate. Weight-adjusting the volumes and clearances significantly improved the accuracy of the pharmacokinetics - An alternative propofol TCI model called Paedfusor, developed by the Glasgow research group, incorporated a preliminary model published by Schüttler and co-workers207 and was recently found to be more accurate than the Kataria model
- Eleveld and colleagues developed a model with an age range between 27 weeks postmenstrual age (PMA) up to 88 years
For sufentanil, the covariate model developed by … and colleagues is accurate with MDPE between … and MDAPE between …, even in patients who are obese
Gepts
−2.3% and 22.3%
18.5% and 29%
For remifentanil, various PK/PD models have been developed, but only the model published by … et al. has been applied in TCI until recently. Evaluation of this model showed an acceptable performance, with an MDPE of … and an MDAPE of …
The … model is based on a data set of nonobese adults. The mathematical limitation of the LBM calculation, as observed for the … model for propofol, is also an issue for the …remifentanil model.
… et al. therefore developed a new model for remifentanil, merging data from several studies including children and nonobese adults
Minto
−15%
20%
Minto
Schnider
Minto
Eleveld
For dexmedetomidine, the … model has been included into clinical TCI pumps.
… et al. published an optimized pharmacokinetic model for administration of dexmedetomidine by target- controlled infusion.
The model was derived from a study involving … adult volunteers, to whom higher concentrations of dexmedetomidine, involving infusion rates above those recommended by the summary of product characteristics, were also administered.
The PK model was enlarged by … et al. to model the various clinical effects of dexmedetomidine in relation to the time course of the plasma concentration as predicted by the … pharmacokinetic model: BIS (with and without non- noxious or noxious stimulation), the Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) score, blood pressure, and heart rate
Hannivoort–Colin
Hannivoort
18
Colin
Hannivoort
