Pharmacokinetics - Exam 3 Flashcards
definition of pharmacokinetics
the mathematical description of the plasma concentrations-time course
dosage regimen
dosage, route of administration, frequency, duration of administration
optimal dosage regimen
effective, nontoxic, without prolonged drug residues in the tissues of food animals
systemic bioavailability
fraction of the dose which reaches the systemic circulation intact; F%, measures extent of absorption
AUC
area under the curve;
F% =
AUC extravascular / AUC IV x 100
the concept of compartments
compartments refers to those tissues and organs for which the rates of uptake and subsequent clearance of are drug similar
4 main compartments
blood, tissue, fat, 3rd spaces
one compartment model
all tissues & organs which the drug penetrates behave as if they were in ready equilibrium with the blood, liner
two compartment model
central and peripheral compartment; curved
rate of distribution
estimated by the distribution phase half life in the 2 compartment model
extent of distribution
measured by apparent volume of distribution (Vd)
Vd is the
volume of distribution, volume of fluid, concentration in plasma in L/kg
for IV administration, Vd=
dose/Cp
for non-IV administration Vd=
dose * F% / Cp
Vd < 1L/kg
limited distribution
Vd = 1L/kg
wide distribution
Vd > 1L/kg
very wide distribution
example of small vd drug
heparin
example of large vd drug
morphine
elimination
drug elimination is measured by 1/2 life or total body clearance (CLb)
half life
t 1/2; time required for the body to eliminate one half of the drug it contains, independent of dose given & route of administration
elimination of most drugs follows
first order kinetics
first order kinetics
means the rate of removal of the drug from the plasma is proportional to the concentration present at a given time, constant percentage, curved
constant percentage
of drug is eliminated per unit time
zero order kinetics
means the rate of elimination remains constant regardless of the amount of drug in the body, constant amount, straight line
after how many half lives is the drug almost all the way excreted
5th
steady state
rate at which plasma concentration of a drug rises to reach a steady state concentration
Cp(ss) is the
steady state [plasma], maintenance rate of drug administration is equal to the rate of elimination
Cp(ss) achieved when
CRI maintenance = rate of elimination
a faster rate does not achieve cpss any faster, only
increase dose does this
plasma clearance (CLp)
volume of plasma cleared of the drug per unit time
renal clearance (CLr)
volume of the plasma cleared of the drug by the kidneys per unit time
CLp equation =
rate of elimination (ml/min)/ plasma drug concentration (mg/ml)
total body clearance CLb
rate of drug elimination from the body by all routes, relative to the concentration of the drug in plasma
increased Vd results in
decreased clearance
increased half life results in
decreased clearance
CLb =
Vd x 0.693 / t 1/2
t 1/2 =
0.693 x Vd / CLb
Cl organ =
Q (blood flow to organ) x E (extraction ratio)
examples of drugs with high hepatic extraction ratio
lidocaine & diazepam
T/F: high first pass effect = high extraction ratio
true
maintenance dose:
dosing rate = CLb x Cp(ss)
loading dose
Vd x desired Cp
if renal disease (insufficiency) present, this will cause ______ in excretion
decrease
change dose or dose interval will help prevent
accumulation
adjusted dose calculation
normal dose x (patient renal clearance / normal renal clearance)
smaller
adjusted dose interval calculation
Dose x F% / CLb x Cp(ss)
larger
renal clearance estimated by
creatinine clearance
rate of elimination equation
mg/min; urine flow (ml/min) x [drug] in urine (mg/ml)
