Unit 2: Pharmacokinetic Modelling Flashcards
1
Q
reduces complexity of pharmacokinetics
A
pharmacokinetic modelling
2
Q
simplification of reality
A
model
3
Q
are models qualitative or quantitative
A
can be qualitative or quantitative
4
Q
general template; something you want to replicate
A
model
5
Q
more variables make a template more ______
A
specific
6
Q
hypothesis using mathematical terms to concisely describe quantitative relationships
A
model
7
Q
wants to predict plasma drug conc
A
pharmacokinetic modelling
8
Q
is pharmacokinetic modelling quantitative or qualitative
A
mathematical/quantitative
9
Q
mathematical description of a biologic system
A
pharmacokinetic model
10
Q
can be used to simulate rate processes describing the movement of drug in the body
A
pharmacokinetic model
11
Q
mathematical tool that allow simulating drug concentration levels in the blood prior to real administration
A
pharmacokinetic model
12
Q
allow more accurate interpretation of the relationship between plasma drug levels and pharmacologic response
A
pharmacokinetic model
13
Q
pharmacokinetic models uses:
predict _______, _______, and ______ drug levels with any dosage regimen
A
plasma, tissue and urine
14
Q
pharmacokinetic models uses:
calculate the optimum dosage regimen for each patient ________
A
individually
15
Q
pharmacokinetic models uses:
estimate the possible _______ of drugs and/or metabolites
A
accumulation
16
Q
pharmacokinetic models uses:
correlate drug concentrations with ________ or _______ activity
A
pharmacologic or toxicologic
17
Q
pharmacokinetic models uses:
evaluate differences in the rate or extent of availability between formulations (________)
A
bioequivalence
18
Q
pharmacokinetic models uses:
describe how changes in _______ or _______ affect the absorption, distribution, or elimination of the drug
A
physiology or disease
19
Q
pharmacokinetic models uses:
explain ______ interactions
A
drug
20
Q
when 2 drugs are able to deliver the same or equivalent bioavailability
A
bioequivalence
21
Q
the # of parameters needed depends on: (2 answers)
A
- complexity of the process (ADME)
- route of drug administration
22
Q
more # of parameters make it (easier/more difficult) to accurately estimate
A
more difficult
23
Q
3 classification of pharmacokinetic models
A
1) empirical
2) compartmental
3) physiological
24
Q
pharmacokinetic models aim to (reduce/increase) complexity
A
reduce
25
simply interpolates the data and allows an empirical formula to estimate drug level over time
empirical models
26
justified when limited information is available
empirical models
27
practical but not very useful in explaining the mechanism of the actual processes
empirical models
28
aka statistical
empirical models
29
main specimen of pharmacokinetic model
plasma/blood
30
model is not factual and does not following the theory at all
empirical models
31
instead of understanding whole ADME, model focuses on experiences of pharmacokineticist and observation on the drug product
empirical models
32
treatment which give drugs without knowing causative agent
empirical treatment
33
does not know the functional group present
empirical formula
34
simple and useful tool
compartmental model
35
simplistic view of drug disposition in the human body
compartmental model
36
provides a simple way of grouping all the tissues into one or more compartments where drugs move to and from the central or plasma compartment
compartmental model
37
most popular model used
compartmental model
38
an assigned place/group of tissues
compartment
39
is not a real physiologic or anatomic region
compartment
40
is considered a tissue or group of tissues that have a similar blood flow and drug affinity
central compartment
41
in a compartment, mixing of drug is _____ and ______
rapid and homogenous
42
considered to be connected to each other by pathways (reversible or irreversible)
compartment
43
two conditions for a central compartment
should have similar hyperfusion (blood flow) and drug affinity
44
administered drug dose is removed from the body by an excretory mechanism as the unchanged drug or as metabolite (kidneys and other excretory organs)
open model
45
all pharmacokinetic models are _________
open model
46
model with a process of elimination and point of exit
open model
47
compartmental model can be divided into 2
open and closed
48
administered drug dose is not removed from the body by an excretory mechanism
closed model
49
drug will persist in the body forever
closed model
50
most common model used in pharmacokinetics
mamillary model
51
useful when little information is known about the tissues
mamillary model
52
one or more compartments around a central compartment – “satellites”
mamillary model
53
drug is both added to and eliminated from a central compartment
open one-compartment model (mamillary model)
54
plasma and highly perfused tissues that rapidly equilibrate with drug
central compartment
55
drug can move between the central or plasma compartment to and from the tissue compartment
open two-compartment model (mamillary model)
56
tissue compartment
peripheral compartment
57
plasma compartment
central compartment
58
total amount of drug in the body = drug in central compartment + drug in tissue compartment
open two-compartment model (mamillary model)
59
rate of elimination/elimination constant
k or k10
60
first order absorption; often from oral route; point of entry
ka
61
apparent first-order rate constant of transfer of drug from the central compartment into the tissue compartment
k12
62
apparent first-order rate constant of transfer of drug from the tissue compartment into the central compartment
k21
63
is the open two-compartment model reversible or irreversible
reversible
64
apparent first-order rate constant of absorption
ka
65
apparent first-order rate constant of drug elimination from central compartment
k or k10
66
significance: enables writing different eq to describe drug conc changes in each compartment
mamillary model
67
compartment 1 has more than 2 satelites
open multi-compartment
68
for multi-compartment model, identify the subscript representation of:
a) central compartment
b) deep tissue compartment
c) shallow tissue compartment
a) 1
b) 3
c) 2
69
apparent first-order rate constant of transfer of drug from the central compartment into compartment 3
k13
70
apparent first-order rate constant of transfer of drug from compartment 3 into the central compartment
k31
71
not all compartments are connected to the central compartment
catenary model
72
significance: visual representation of rate processes (first order and zero order)
mamillary model
73
significance: estimate the number of pharmacokinetic constants are necessary to describe the process adequately
mamillary model
74
everything is connected to central compartment
mamillary model
75
connection of compartments is like a chain/train
catenary model
76
does not apply to the way most functional organs in the body are directly connected to the plasma
catenary model
77
are assigned and are not constant in a model
compartments
78
aka blood flow or perfusion model
physiologic pharmacokinetic model
79
based on known anatomic and physiologic data
physiologic pharmacokinetic model
80
realistic means of modeling tissue drug levels
physiologic pharmacokinetic model
81
disadvantage: it is difficult to acquire tissue samples to measure drug concs
physiologic pharmacokinetic model
82
advantage: modelling tissue drug levels are accurate as it is close to realistic
physiologic pharmacokinetic model
83
each tissue volume must be obtained and its drug concentration described
physiologic pharmacokinetic model
84
on physiologic pharmacokinetic model --> if there’s no perfusion, ______ is excluded
organ (e.g. brain, bones, others parts of CNS are often excluded)
85
the # of tissue compartments varies with drug
physiologic pharmacokinetic model
86
tissue drug conc of which drugs (4) has been described by the perfusion model
digoxin, lidocaine, methotrexate, thiopenthal
87
1. The size of the organ tissue
2. Blood flow to the organ tissue
3. The experimentally determined ratios of drug concentration between the tissue and the blood
factors that predict conc of drug in tissues in physiologic pharmacokinetic model
88
physiologic pharmacokinetic model:
relationship of organ to drug concentration
directly proportional
89
physiologic pharmacokinetic model:
relationship of blood flow to drug concentration
directly proportional
89
physiologic pharmacokinetic model:
relationship of blood flow to absorption
directly proportional
90
organs are represented instead of compartments
physiologic pharmacokinetic model
91
physiologic pharmacokinetic model:
represents the rate of blood perfusion to the tissue
Q
92
liver and kidney are (highly/lowly) perfused organs
highly
92
liver and kidney are (highly/lowly) perfused organs
highly
93
physiologic pharmacokinetic model:
represent kinetic constants
ks
94
physiologic pharmacokinetic model:
is the first-order rate constant for urinary drug excretion
ke
95
physiologic pharmacokinetic model:
is the rate constant for hepatic elimination
km
96
physiologic pharmacokinetic model:
RET means
rapidly equilibrating tissue
97
physiologic pharmacokinetic model:
SET means
slowly equilibrating tissue
98
liver and kidneys belong under (RET or SET)
RET
99
advantage: information derived from these models can be applied to several species (humans, experimental animals)
physiologic pharmacokinetic model
100
disadvantage: fewer data points than parameters that one tries to fit and therefore projected data are not well constrained
physiologic pharmacokinetic model
101
disadvantage: data can be experimentally difficult to obtain
physiologic pharmacokinetic model
102
disadvantage: data can be affected by pathophysiologic conditions which can cause variation to blood flow, tissue size, drug tissue-blood ratios
physiologic pharmacokinetic model
103
actual tissue volume is used
physiologic pharmacokinetic model
104
estimated tissue Vd (volume of distribution) is used
compartmental model
105
experimentally determined in ANIMALS --> extrapolated to humans
physiologic pharmacokinetic model
106
no data fitting required
physiologic pharmacokinetic model
107
in physiologic pharmacokinetic model:
drug concentrations in various tissues are predicted by (3)
organ tissue size, blood flow, experimentally determined drug tissue- blood ratios
108
2 ways to measure drug concentration
HPLC, Mass spectrometry
109
HPLC meaning
high performance/high precision liquid chromatography
110
ways to retrieve biologic specimen (2)
invasive and noninvasive methods
111
retrieval of biologic specimen:
requires parenteral or surgical intervention in the patient
invasive
112
retrieval of biologic specimen:
needs insertion or cutting open a patient
invasive
113
retrieval of biologic specimen:
operation, anaesthetics
invasive
114
retrieval of biologic specimen:
blood, spinal fluid, synovial fluid, tissue biopsy
invasive
115
retrieval of biologic specimen:
urine, saliva, feces, breastmilk
noninvasive
116
retrieval of biologic specimen:
can be obtained without parenteral or surgical intervention
noninvasive
117
biologic specimen:
most direct approach, most used to measure drug conc in body, most accessible invasive part
plasma
118
biologic specimen:
total plasma drug concentration
unfiltered plasma
119
biologic specimen:
unbound drug concentration
filtered plasma
120
biologic specimen:
indirect method to ascertain bioavailability
urine
121
biologic specimen:
drug that has not been absorbed after an oral dose
feces
122
biologic specimen:
has been biliary secreted after systemic absorption
feces
123
biologic specimen:
unbound drug, noninvasive
saliva
124
biologic specimen:
determination if drug reached the tissues at right concentration
tissue
