Flashcards in Pharmacokinetics Deck (74):

1

## what is pharmacokinetics

### the study of the time course of drug concentration in the body, usually as reflected in the plasma concentration (fate of drug in the body).

2

## first order kinetics is also referred to as what

### exponential kinetics characterized by a constant fractional change per unit time

3

## first order kinetics is measured as what

### the rate constant (Ke)

4

## zero order kinetics is also referred to as what

### saturation kinetics

5

## first order kinetics is characterized by what

### a constant amount of change per unit time

6

## half-time or biological half life (t 1/2)

### for drugs that are eliminated by first-order kinetics, the fractional change in the amount of drug in the blood is generally expressed by the half-life. Time required for 50% of the drug remaining in the body to be eliminated (or the time required for the blood concentration to decrease 50%).

7

## rate constant of elimination (Ke)

### For drugs that are eliminated by first-order kinetics, the rate constant is the fractional change per unit time (fraction/min, fraction/hour, etc)

8

## rate constant of elimination (Ke) is equal to what

###
0.693 / t1/2

OR

t1/2 = 0.693/ke

9

## what is clearance

### the quantification of elimination

10

## for most drugs in clinical setting, clearance is

### constant

11

## clearance represents the volume of

### biological fluid that would have to be completely freed of drug to account for the rate of elimination (ie. the volume of body fluid processed in a given time)

12

## clearance is expressed as

### volume per unit time

13

## individual organ clearances are

###
additive

ie. take renal cl, pulmonary cl etc. and add the volumes up to give you total systemic clearance

14

## clearance can be calculated from what

###
1. excretion rate/concentration

2. dose/area under the curve (AUC)

15

## compartmental model of pharmacokinetics

### uses selected model to "fit" parameters to data

16

## noncompartmental model of pharmacokinetics

### most use the same basic principles (Trapezoidal rule; observed data; calculated elimination rate constant; standard formulas for the rest)

17

## Fate of a drug

###
1. liberation

2. absorption

3. distribution

4. metabolism

5. excretion

18

## what is liberation

### release from matrix

19

## what is absorption

### process and rate

20

## what is distribution

### movement in body

21

## what is metabolism

### removal by biotransformation

22

## what is excretion

### physical removal from body

23

## what are key pharmacokinetic parameters

###
-clearance

-volume of distribution

-half-life

-bioavailability

24

## what is volume of distribution

### concept for a given dose, the theoretical size necessary to produce a specific calculated exposure

25

## what is half-life

### the length of time necessary to reduce or "eliminate" 50% of the current level of drug

26

## what is bioavailability

###
the fraction of the dose that reaches systemic circulation

f=1 for IV

27

## assumptions of a one compartment model

###
-the body is a single compartment with a volume (V) and drug concentration (C)

-distribution of drug is uniform and rapid compared with absorption and elimination

-elimination of the drug conforms to 1st order kinetics

28

## see diagram: slide 10-11

### see diagram: slide 10-11

29

## assumptions of a two compartment model

###
-the body contains 2 compartments, central and peripheral

-all kinetics are first order

-elimination is form the central compartment

30

## see diagram: slide 12 + 13

### see diagram: slide 12 + 13

31

## what are model independent parameters

###
-clearance, half-life, Vd

-AUC

-Cmax (max concentration)

-Tmax (time of max concentration)

32

## see calculations: slide 16

### see calculations: slide 16

33

## what is the plateau principle

###
-when a drug is administered intravenously, the plasma concentration will increase until the rate of elimination and administration are equal

-at that point, the plasma drug [ ] will remain constant until there is a change in the dosage rate of elimination kinetics

34

## steady state concentration (Css) equation

### rate of administration/total body Cl = dosing rate/Cl

35

## dosing rate equals

### Cl x Css

36

## Css equals

### dosing rate/Cl

37

## see diagram: slide 19

### see diagram: slide 19

38

## time required to achieve steady state depends on

### half life

39

## how many half lives does it take to achieve steady state

### 4-6 half-lives

40

## see diagram: slide 21

### see diagram: slide 21

41

## conditions for fixed rate, multiple doses

###
-the drug will accumulate in the body if the time interval between doses is less than 4 half lives

-total body stores of the drug increase exponentially to a plateau

-the plasma [ ] will fluctuate during the dosing interval

-Css now represents the mean [ ] of the drug during the dosing interval

42

## for oral dosing, what will also influence Css

### bioavailability

43

## what is bioavailability

### is the fraction (f) of the administered dose that reaches the systemic circulation

44

## what is the equation of Css in a fixed rate, multiple dose regimen

### Css = (f) x dose / (dosing interval x Cl)

45

## what happens to the [plasma] with a fixed rate multiple dose regimen

### [plasma] will fluctuate btwn a maximum (peak) and a minimum (trough) concentration

46

## see diagram: slide 24

### see diagram: slide 24

47

## for therapy characterized by repeated intermittent dosing, the choice of dosage interval is based on what

###
-tolerance btwn dose variations of serum concentraions (based on half life and toxicity of the drug)

-patient convenience plays a role for out patient therapy

48

## when would a loading dose be administered

### when the time to reach steady state is needed immediately

49

## the amount of drug required to achieve a given steady-state value in plasma is the amount that

### must be in the body when the desired steady-state is reached

50

## what variable relates the total drug [ ] in the body to the plasma [ ]

### Vd

51

## loading dose equation is

### loading dose = Css x Vd

52

## what is nonlinear, dose-dependent or saturable elimination kinetics

### a capacity-limited process where drugs exceed the metabolic/excretory capacity of the body to eliminate that drug as a linear rate

53

## describe the clearance rate of a nonlinear elimination

### Cl will vary with the [ ] of drug in a manner analogous to the M-M equation for enzyme kinetics

54

## virtually all drugs taken by pregnant women are transferred to some degree across the

### placenta to the fetus

55

## delivery of single doses in pregnant women is limited by what

### blood flow to the placenta

56

## when does peak fetal blood concentration occur

### btwn 20 mins and 4 hrs after IV dosing depending on the chemical characteristics of the drug

57

## chronic dosing during pregnancy can lead to what

###
a steady-state

fetal:maternal [ ] approach unity

58

## what are 5 critical time frames of pediatric pharmacology

###
1. conception to birth

2. birth to 1 month

3. 1 month to 2 yrs

4. 2 years to 12 yrs

5. 12 yrs to 18 yrs

59

## what drug characteristics affect developmental factors

###
-drug absorption

-drug distribution/% body water

- drug metabolism

-drug excretion

60

## dosages are determined by

###
-formula

-body to surface area

61

## drug disposition and aging is determined by what

###
-absorption

-distribution

-drug metabolism

62

## how is absorption affect by age

### relatively normal

63

## how is distribution affect by age

### aging is characterized by decreased lean body mass, increased % of body weight represented as fat, and decreased total body water

64

## how is drug metabolism affected by age

### -slower on average in the elderly due to decreased hepatic blood flow and smaller liver size

65

## does the aging liver decreases its metabolism for all drugs

### the aging liver to metabolize drugs does not decline in a similar way for all pharmacological agents, and the clearance of some drugs is largely unchanged (depends on intrinsic Cl)

66

## what is the cockroft-gault equation

###
-estimates the glomerular filtration rate and generally

-obtained by estimating endogenous creatine clearance

67

## what is cockroft-gault equation

### CreatineCl = [140-age] [weight] / (72 x serumcr in mg/dL)

68

## for women, creatinine clearance is --% of the value calculated by the Cockroft-Gault eqn

### 85%

69

## why might the GRF be overestimated using the Cockroft-Gault eqn in older individuals with low [ ]

### bc endogenous creatinine production from muscle is decreasing with age

70

## how does age affect renal excretion

### -aging is associated with decreased renal size and renal blood flow, leading to decreases in glomerular filtration rate

71

## decreases in tubular function parallel those in

### glomerular function

72

## based on cross-sectional studies, creatinine clearance decreases an average of

### 8ml/min/decade after age 30

73

## what dosage adjustments are done for renal dysfunction

###
1. decrease dose, but maintain dosage interval

2. maintain dose, but increase length of dosage intervals

74