Pharmacokinetics Flashcards
What is the fundamental hypothesis of pharmacokinetics?
There is a predictable relationship b/t plasma (or serum) concentration of a drug and its effect
Rate of elimination equation
Rate = (Vmax * C) / (Km + C)
WRT elimination, if the system is not saturated, what happens with increasing concentration?
increasing concentration increases elimination
Absolute rate
mg/hr
changes as drug concentration changes
Fractional rate
fraction/hr
stays constant
First assumption for models
Elimination must be first order
Second assumption of models
instant distribution
What happens as steady state?
rate in = rate out
dose/dose interval = elimination/dose interval
What are the primary pharmacokinetic parameters?
Volume of distribution
Clearance
Bioavailablity
What pharmacokinetic parameters are derived?
half-life
Ke
Volume of distribution
Volume of a sample fluid required to explain dilution of dose given
Vd = dose / concentration at time zero
What are some causes of non-uniform distribution of solutions WRT Vd?
- Ion trapping - i.e. weak bases accumulate inside cells
- protein binding in plasma
- tissue: plasma partition coefficients
What adjustments can be made WRT Vd?
- For “ideal body weight” – e.g. obese patients would not follow typical formula
- Pathologic conditions – e.g. edema, ascites
Clearance (Definition and equation)
Clearance is the virtual volume that is freed of drug per unit time
CL (L/hr) = Rate of absolute elimination (mg/hr) / conc. (mg/L)
Clearance - calculation using dose
CL (L/hr) = Dose (mg) / AUC (mg*hr/L)
AUC = area under the curve
Extraction Ratio (definition, #, equation)
Most direct measure of organ function
# 0-1 Varies with functional state of organ
ER = (Cin - Cout) / Cin
Clearance - calculation using ER
CL (L/hr) = ER * Blood flow (L/hr)
Ke - elimination rate constant
The fraction of drug that is removed per hr
Ke = CL / Vd
Half life equation
t_1/2 = 0.693 / Ke
Bioavailability (F)
FRACTION of drug administered that reaches the CENTRAL CIRCULATION
F = f * (1 - ER)
f ~ 1.0 – its the fraction absorbed into portal circulation
Accumulation vs Elimination
The time it takes to accumulate to steady state is the same time it take to eliminate the drug
Both of these are determined using half life
5 half lives accumulates/eliminates 97% of final/total
Accumulation Factor (Ra)
Ra = 1 / (fraction lost in one dosing interval)
Fraction remaining equation
e^(-Ke * T)
T = dose interval
Estimated concentration after the first dose is administered
Cp(0) = F * D / Vd
Dosing rate (calculation)
CL * Css
Calculation for adjusting dosing regimen based on actual effect of first dose
New Rate = Old Rate * (Desired Css / Measured Css)
(mg/hr) (mg/hr) (mg/L) (mg/L)
Loading dose (equation + use)
Loading dose = Vd * Target concentration
Used when you need to reach the peak quickly
Concentration equation for a one-compartment model
-Assumptions
Cp(t) = A * (e^(-Ke * t))
Assumptions
- Must be first order process
- Body ONE homogenous compartment
- instantaneous mixing
Equations for Css(max) and Css(min)
Css(max) = (F * D / Vd) * Ra
Css(min) = Css(max) * Fraction remaining at T
