EXAM 1 Flashcards
kinetic homogeneity
The predictable relationship between plasma drug concentration and the concentration at the site of action
–>we assume that the plasma drug conc. directly relate to concentrations in the tissues
biopharmaceutics
the interrelationship of the physicochemical properties of a drug, the dosage form in which the drug is given, and the route of administration on the rate and extent of systemic absorption
pharmacokinetics
study of the time course of the drug process that determines the concentration of drugs in body fluid and tissues over time
clinical pharmacokinetics
The application of PK principles to the safe and effective therapeutic management of drugs in an individual patient
pharmacodynamics
the study of the detailed mechanism of action by which drugs produce their pharmacological effect. Refers to the relationship between the drug conc. at the site of action and the resulting effect
therapeutic drug monitoring
measurement of drug concentrations and assessment and application of the resulting concentrations to design safe and effective drug regimens
population-based mathematical model
determination of parameters based on population PK/PD information, clinical trial data, and patient clinical and/or demographic data
patient-specific mathematical model
the utilization of patient-specific drug concentration data to determine PK/PD parameters and individualize the drug regimen
one compartment model
all uniform distribution
drug dose–> compartment–> elimination
-Absorption is instantaneous and complete
zero order elimination
the amount of drug eliminated does not change with the amount of drug/concentration in the body
-the amount removed remains constant
-the FRACTION of drug eliminated
VARIES
first-order elimination
the amount of drug eliminated in a certain period is directly proportional to the amount of drug in the body
-the FRACTION of a drug eliminated remains CONSTANT
Elimination rate constant
-Ke
-always a negative number
what does the elimination rate constant tell you
the fraction or percentage of the drug dose administered that is removed per unit of time
half-life equation
=0.693/Ke
cmax equation
dose/Vd
elimination rate constant equation
(Ln Cp1/Cp2)/t
Factors affecting drug movement
molecular size and structure
degree of ionization
lipid solubility
binding affinity to serum and tissue proteins
drugs affinity for a tissue component
passive diffusion
rate is proportional to drug concentration gradient, partition coefficient, and SA for absorption
Active transport
carrier mediated
requires a form of energy
facilitated diffusion
carrier mediated
does not require energy
Movement occurs down a concentration gradient
surface area effect on absorption
small surface area=decreased absorption
duodenum and jejunum are optimal for absorption
GI factors that affect drug absorption
surface area
pH
motility
gastric emptying
perfusion
food
disease
bioavailability
fraction of the unchanged drug dose that is absorbed from the drug product and reaches the systemic circulation
bioavailability equation
F=amount of drug reaching systemic circulation/total amount of drug dose
extraction ratio
provides a direct measurement of drug removal from the liver following oral administration of a drug
extraction ratio equation
=(drug concentration in the blood entering the liver-drug conc. leaving the liver)/ drug conc. in the blood entering the liver
extraction ratio represents
the amount of drug that is removed by the liver before it is available for systemic circulation
Modified released characteristics compared to IR
Tmax longer
Cmax reduced
AUC identical
Steady-state equation
(Cpss)=(dose x F x S)/(Tau x Cl)
What does S represent
represents the fraction of the administered dose which is the active drug when administered as a salt or ester formulation
S equation
S=MW of parent drug/total weight
factors affecting drug distribution
cardiac output
regional blood flow
membrane permeability
tissue volume
Regional physiological pH changes
disease states altering physiological factors
solute carriers
Oligopeptide transporter
Organic anion transporter protein
Organic cation transporter
ATP-Binding Cassette
MDR1 or P-glycoprotein
distribution constant equation
Kd=organ blood flow (Q)/ [volume of the organ (V) x Ratio drug concentration (R)]
large Q does what to distribution time
decreases distribution time
large tissue volume (V) does what to distribution time
increases distribution time
-longer time needed to fill a larger volume
partition coefficient
physical property that measures the ratio of the solubility of the drug in the oil phase to the solubility in the aqueous phase
partition coefficient equation
Log P= Log (Coil/Cwater)
R ratio
concentration in tissue/concentration in plasma
higher R-value indicates
increase in time to equilibration between tissue and plasma
larger R-value associated with
larger Vd
slower Kd
longer t1/2
tissue affinity and binding to proteins within myocardium
limiting processes of drug distribution
concentration gradient
membrane thickness
membrane surface area
lipid solubility/partition coefficient
diffusion constant
perfusion limited distribution
rate of drug delivery from circulation to the tissue is largely dependent upon blood flow to that tissue
perfusion limited distribution rate-limiting step
blood flow
permeability limited distribution
drug distribution is limited by the slow diffusion of the drug across the membrane in the tissue
volume of distribution
indicator of the extent of drug distribution into the body fluids and tissues
volume of distribution equation
Vd=dose/drug concentration in system after equilibrium
loading dose equation
=Vd(desired Cp)/(F x S)
smaller Vd from
high water solubility
increased plasma protein binding
decreased tissue binding
larger Vd from
high lipid solubility
decreased plasma protein binding
increased tissue binding
percent protein binding equation
={total drug concentration-Cp(unbound)/total drug conc.} x 100
factors that affect protein binding
drug concentration
affinity of the protein for the drug
The concentration of the circulating protein
The number of binding sites available
presence of disease or altered physiologic state
presence of other protein-bound drugs
physicochemical properties of the drug
elimination
irreversible drug removal from the body results from the processes of metabolism and excretion
two major organs involved in the elimination
kidneys and liver
drug clearance
removal of drug from a volume of plasma or blood in a given time
Compartmental model clearance equation
Clt= Vd x Ke
physiological model clearance equation
Clorgan=Q x ER
factors affecting clearance
body weight, SA and comp.
cardiac output
organ function
drug-drug interactions
extraction ratio
genetics
plasma protein binding
clearance equation
= dose x F x S/Tau x average Cpss
steady state
as the rate of elimination approaches the rate of administration, the max and min concentrations will reach an equilibrium when no additional accumulation will occur
