Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biopharmaceutics & pK > Clinical Pk > Flashcards

Clinical Pk Flashcards

1
Q

what is responsible for the variability in response to drugs between patients

A

different Cp (plasma concentration of drug)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

the variability in drug plasma concentration of drugs is especially important for drugs with (3 words) because____

A
  • narrow therapeutic index
  • the dose that is effective is very close to the dose at which toxic effects occur, i.e. ratio of the minimum toxic plasma level to the minimum effective dose is very small
    • little room for error
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how are drugs with narrow therapeutic index managed medically

A

through drug plasma level monitoring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

name 4 classes of drugs for which plasma level monitoring is common, provide examples for each class

A
  • Antiarrhythmic Drugs
    • e.g. Procainamide
  • Antibiotics
    • Vancomycin
  • Anticonvulsants
    • phenytoin
  • Psychotropics
    • lithium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are the 2 key parameters that need to be known to determine the mean steady state plasma level (Cpss)

A
  • volume of distribution (V)
  • elimination rate constant (K)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is this equation and what do each of the variables stand for

Cpss = FD/tau x Cl = FD/(tau x K x V) = FD t1/2/ (tau x 0.693 x V) where

A
  • Drug plasma concentration at steady state
  • F = bioavailability
  • D = dose of drug administerd
  • tau = dosage interval
  • Cl = clearance
  • V = volume of distribution
  • K = loss rate constant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Dose adjustment may be warranted when the following physiological factors exist (3)

A
  • weight issues
  • chronic heart failure
  • renal or liver issues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

renal function is assessed or measured by

A

creatinine clearance (Clcr)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

creatinine is eliminated almost exclusively by

A

glomerular filtraton

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what will impairment of glomerular filtration result in

A
  • decrease in excretion rate of creatinine,
    • i.e. decrease in Clcr, and serum creatinine concentration rises
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

although creatinine clearance can be calculated, this biomarker is most often used to measure renal function

A

serum creatinine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Serum creatinine is inversely related or directly proportional to glomerular function?

Describe the equation

A
  • inversely related
  • Clcr = k0/SCC where
    • SCC = serum creatinine
    • ko is the constant rate of production of creatinine in the body
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

as it relates to the equation below, when renal or kidney function decline, serum creatinine decreases or increases

Clcr = Ko/Scc

where Scc = serum creatining

Ko = rate constant - production of creatinine in the body

A

decreases because serum creatinine levels are inversely proportional to glomerular filtration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

these tools used by physicians (what are these?) relate creatinine clearance to serum creatinine, gender, body weight and height are are used to

A
  • nomograms
  • calculate the dose for the patient based upon the estimate of creatinine clearance from serum creatinine levels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

biomarkers for metabolic (liver) function are readily available (true/false)

A

false

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

when liver function is reduced, drug metabolism is severly or mildly impacted

A

mildly

17
Q

when studies are conducted in normal healthy volunteers, what are the issues with dosing and dosing regimen as it relates to use in real life. Why?

A
  • the study doesn’t mimic the pt population that will use the drug i.e. healthy volunteers compared with disease state patients
  • limited ethnicities or underrepresentation of gender
  • comorbid conditions and con-meds excluded
  • well controlled parameters for trials
18
Q

Population pharmacokinetics looks at

A

ways to obtain more representative estimates of pK parameters in different pt populations

19
Q

what are the three clinical study phases, what do they typically assess

A
  • Phase I studies
    • small study 12-100 subjects
    • healthy volunteers, intensive sampling, calculate mean values
    • safety study
    • sub therapeutic dose but with dose ranging/ascending dose
  • Phase II
    • 100 - 300 subjets
    • disease state
    • safety and efficacy at therapeutic dose
  • Phase III
    • large study
    • disease state, less sampling
    • efficacy, effectiveness, safety
    • estimate population parameters
20
Q

What are 3 statistical approaches to estimation of pK parameters

A
  • Conventional
    • non-compartmental analysis
    • model fitting by non-linear regression
  • Multiple regression analysis
  • non-linear mixed effect modelling
21
Q

the conventional approach to estimation of pK parameters determines population parameters by

A
  • intermediate estimation of parameters in each member of a group of individuals
22
Q

what are common pk parameters measured or analyzed via the conventional approach

A
  • mean and std deviation for each parameter
    • e.g. gender, ethnic group, responders/non-responders
  • Clearance (Cl); Volume of distribution (Vd); Plasma concentration (Cp)
23
Q

how are pk parameters estimated in the conventional approach (2 statistical methods)

A
  • non-compartmental analysis
  • model fitting using non-linear least squares regression analysis
24
Q

this statistical method does not require a specific model​

A

non-compartmental analysis

25
Q

what pK parameters is noncomparmental analysis based upon (4)

A
  1. AUC
  2. Cp vs time
  3. slope
  4. terminal beta phase
26
Q

what 4 pK parameters are calculated in noncompartmental analysis

A
  1. AUC
  2. Vd
  3. Cl
  4. halflife
27
Q

True/False:

Model fitting fits the selected pK model to pk response data (Cp and t) and attempts to provide parameter estimates that minimize differences between observed and predicted values

A

True

28
Q

Error or variability in model fitting is a result of (3)

A
  • random error relating to independent variables (time) e.g. errors in recording of drug administration time
  • random errors related to dependent variables (Cp) e.g. assay measurement
  • intraindividual variation
29
Q

to account for errors and avoid bias the model is linked to a ____________model

A

variance

30
Q

Nonlinear least squares regression analysis is an iterative process that modifies parameters until criterial for good fit are met. This is done by fitting non linear data to

A
  • differential and integrated equations (NonLin)
  • extended least squares method (Elsfit)
31
Q

Multiple regression analysis using SAS or SPSS do this

A

determines the impact of demographic, phsiological and pathological factors on pK

32
Q

SPSS multiple regression analysis assesses

A
  • the relationship b/t pk parameters (Vd, Cl) and predictors (age, sex etc)
  • calculates contribution of each predictor to the pK parameter
  • tests signficance
33
Q

SAS allows development of

A
  • predictive models for pk parameters
  • considers all regressions and generates model with highest R2
  • uses predicted sum of squares for model selection
  • max adjusted R2 models compared with othe models
  • model with minimum predicted sum of squares with fewest independent variables chosen
34
Q

the model that fits a pk model to all data obtained from pooled pts and includes randomly treated errors as well as unusual errors in analysis is called:

what is another name by which it is known as

A
  • Non-linear fixed effects modeling (NonMem)
  • First order method
35
Q

what is an advantage and disadvantage of the first order method

A
  • advantage - do not need a lot of pk data
  • disadvantage - need large number of subjects
36
Q

what are common sources of error that cause biased estimates in population pK parameters

A
  • Fixed Effects
    • pt characteristics (age, weight, height, gender)
    • underlying pathology (comorbid conditions)
    • concomitant therapy, alcohol intake, smoking
  • Random Effects
    • amount of pK variability
      • interindividual variation (n)
      • intraindividual variation (assay error)
37
Q

NonMEM analyzes poole data and deals with the concomitant effects on parameter estimation through determination of (3)

A
  • mean values of pk parameters
  • quantiative relationship to subjects
  • variability across population

Biopharmaceutics & pK (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions