Pharmacokinetics Flashcards
First order kinetics
Most common
Rate of process is proportional to concentration
(Exponential) - gets slower over time
Rate can be expressed as constant fractional change per unit time
t1/2
.7/k
Time required before 50% completion of the process
Number of half lives to “complete” elimination process
5 half lives (97% eliminated)
Zero order kinetics
Rate of process is independent of drug concentration
Not common: constant IV, ethanol, high dose aspirin, phenytoin
**mech of elimination or absorption reaches a level of saturation - rate is constant
Increased risk of toxicity
Mass-law kinetics
Mixed order
Zero order until certain concentration (above/below saturation) is reached and first order takes over
Volume of distribution
Volume of fluid in which drug would be distributed assuming that it existed throughout that volume at the same concentration as in plasma
Vd = loading dose/plasma conc of drug
Loading dose
To get desired plasma concentration quickly
Vd x initial plasma concentration (desired concentration)
Larger Vd
Requires longer time of elimination
Total body clearance
Apparent volume of fluid from which drug is totally removed per unit time
CL = Vd x ke
Describes combined efficiency of all elimination pathways
Smaller Vd
Could be highly bound to proteins
Increase Vd for drug with high protein binding
Decreased liver function - less protein available for binding
Decrease Vd for drug with high protein binding
Decreased kidney function - less elimination
Peak concentration of single dose
Proportional to dose
Duration of concentration of single dose
Only increases as a function of half life
Doubling dose will increase duration but it will not double duration
Time of peak concentration of single dose
Independent of dose
Decrease Ka, increase time to reach peak conc
Differences in Ka
Of greater importance for drugs used in depot preparations
Impaired elimination
Prolongs concentration but doesn’t effect peak concentration
Rate of elimination
More important than absorption
Multiple dose timing very sensitive to elimination
Decrease in Ke will Increase half life
Plateau principle with repeated doses
Rate of input - zero order
Rate of output - first order
Accumulation and elimination both take 4-5 half lives - depends only on elimination
Doubling dose, doubles plateau
Accumulation time to plateau
Independent of dose
Plateau state and impaired elimination
Increase in proportion to the degree of impaired elimination
How long does it take to achieve new half life
5 elimination half lives
Less variation in plateau
Smaller doses more often
*Sometimes harder to have patient compliance and need to adjust to bigger doses less frequently
Larger doses more frequently
Greater risk of toxicity/adverse side effects even though average plateau is the same
Adjust to impaired elimination
Reduce dose or increase interval
Avoid unnecessary medication
Deviations from elementary model
Active metabolites may have different time course than parent drug
Delayed effect
Different kinetics in different compartments
Varying renal and hepatic function
Mass lass kinetics
Zero order elimination
Slowing rate of absorption
Blunts the fluctuations around the plateau
Bioavailability
Fraction of dose that is absorbed and reaches circulation as active drug
AUC oral/AUC IV
Affected by route of administration, solubility, first pass, degradation in intestinal tract
Plateau concentration equation
Css = (F)(Dose rate)/Cl
Css = (F)(Dose rate)(t1/2) / (.7)(Vd)
