Pharmacokinetics 1 + 2 Flashcards

1
Q

what is pharmacokinetics (PK)?

A

what the body does to the drug (ADME)

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2
Q

what is pharmacodynamics?

A

what the drug does to the body i.e. mechanism of action

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3
Q

what are the stages to collecting and analysing PK data?

A
  1. drug is administered
  2. Blood sample is taken
  3. Analyse the blood via HPLC or LC-MS or Atomic absorption spectrometry
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4
Q

what are the main types of pharmacokinetic (PK) data analysis?

A
  • Non-compartmental analysis
  • Compartmental
  • Population PK models
  • Physiologically-based (PBPK) (bottom-up approach)
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5
Q

what is the straight line equation of PK drug elimination?

A
C = -k.t + Co
C = Conc
K = rate constant
t = time
Co = conc at time zero

(negative sign showing the loss of the drug with time (so a negative line gradient)

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6
Q

what is zero order process of drug elimination?

A

elimination of a constant amount of drug per unit of time, independent of drug concentration

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7
Q

what is first order process of drug elimination?

A

constant proportion of drug eliminated in a defined time period

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8
Q

what is absorption?

A

the transfer of an exogenous compound (i.e. drug) from site of
administration into the systemic circulation

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9
Q

what type of compounds cross cell membranes easier and are rapidly absorbed?

A

lipid-soluble compounds

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10
Q

what parameters are looked at when talking about absorption?

A

Cmax and Tmax

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11
Q

what is the trapecoid rule to calculate area under the curve?

A

the sum of the area of all the trapezoids using this equation: (C1+C2)/2 X (t2-t1) to work out the area of one trapezoid

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12
Q

what is bioavailability a measure of?

A

the extent of absorption after extravascular administration

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13
Q

how do we calculate bioavailability?

A

(% of parent drug in urine after oral dosing) / (% of parent drug in urine after IV dosing)

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14
Q

what determines the distribution of drugs into tissues from the blood circulation?

A

– Its ability to cross cell membranes (based on physiochemical properties)
– Blood flow to individual tissues
– Extent of its plasma protein binding

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15
Q

what effect does drug binding to plasma proteins have?

A

it increased the volume of distribution as if it’s bound to proteins it won’t be able to diffuse into tissues

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16
Q

how do we calculate volume of distribution?

A

(total amount of drug in body) / (conc of drug in blood)

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17
Q

what does a volume of distribution of <3L mean?

A

drug is mostly in plasma

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18
Q

what does a volume of distribution of ~40L mean?

A

even distribution of the drug throughout the body

19
Q

how do we calculate half-life?

A

t1/2 = 0.693/K

where K= Clearance / vol od distribution

20
Q

how many half-lives does it take usually for a compound to reach steady state?

A

5 half-lives

21
Q

what are the features of a compartmental fit/model?

A
  • use exponential equations to describe the curve
  • accomplished by theoretical compartments and transfer rates
  • Can be used for simulations (to an extent)
22
Q

what is the one compartment model?

A
  • assume it’s a linear process

- all tissues and organs are lumped into one compartment

23
Q

what is the two-compartment model?

A
  • assumes the body doesn’t conform to one compartment
  • represent a group of similar tissues or fluids
  • more flexibility
24
Q

what is the ‘central’ or ‘peripheral’ compartment?

A

-a compartment including blood, heart, lungs, liver and kidneys

25
what are the features of population pharmacokinetic models?
- intensive and sparse sampling - computationally intensive - longer analysis time - allows provision for PK/PD modeling
26
what are advantages of individual PK analysis methods?
1. simple 2. robust 3. model-independent 4. user-friendly 5. rapid
27
what are disadvantages of individual PK analysis methods?
1. assumes linear PK 2. Single analysis - cannot address multiple doses 3. study design often limits analysis 4. model - independet
28
what are advantages of population PK analysis methods?
1. robust 2. provides structural model for PK/PD 3. Any route of admin 4. Linear and non-linear PK supported 5. descriptive and predictive 6. studies can be pooled
29
what are disadvantages of population PK analysis methods?
1. less rapid 2. less user-friendly software 3. more expertise required for analysis
30
What is PBPK and how is it different from ‘traditional’ | PK approaches?
- traditional PK approaches lump kinetically similar tissues together in a way that typically bears no relation to anatomical structure or physiology - PBPK has compartments representing organs or tissues whose drug conc are assumed to be uniform
31
what can we use the PBPK model approach for?
- simulation of clinical trials without the need for clinical data - estimation of tissue specific drug concentration - assessment of potential for drug-drug interactions
32
what effect does a change in dose have on non-linear pharmacokinetics?
- causes a disproportionate change in AUC | - affects metabolism, transport(distribution) and absorption
33
true or false: 'the rate of elimination is not proportional to the concentration or to dose given'?
True
34
what is the role of pharmacokinetics in drug development?
to look at: • In vivo (animal models) • In man (phase I clinical trial – first in man) • In clinic (several stages of clinical trial before drug approval)
35
why can small animals tolerate relatively larger doses?
as they have a more rapid clearance rate.
36
what factors are considered when you individualise a dose?
– Renal function – Hepatic function – Genetics
37
what is used to help predict drug action/metabolism?
– Liver function tests – Marker compounds – Pharmacogenetics
38
what are you testing for in liver function tests?
-bilirubin levels -liver function enzymes (if these are raised, shows a sign of hepatic dysfunction)
39
what is Pharmacogenetics?
Study of how genetic variations affect drug response
40
in therapeutic drug monitoring, what is monitored in the clinical trials?
efficacy and toxicity
41
in therapeutic drug monitoring, what is monitored in the lab tests?
pharmacokinetics, pharmacodynamics and pharmacogenetics
42
what are the characteristics of drugs with a potential for therapeutic dose monitoring?
(i) variable or unpredictable relationship between dose and resulting plasma drug concentrations (ii) narrow therapeutic window (iii) ability to correlate measured drug concentration with efficacy and/or toxicity (iv) availability of reliable and clinically feasible assays
43
what is 'therapeutic window'?
``` - range of drug exposures that produce a therapeutic response without causing any significant adverse effect in patients (the range between minimum effective concentration and minimum toxic concentration) ```