Pharmacokinetics Flashcards
pharmacokinetics
what body does to drug
ADME
pharmacodynamics
what drug does to human body
drug absorption oral
oral
stomach
small intestine
through hepatic portal vein
liver
part recycles from liver to small intestine
part goes liver to systemic circulation
passive diffusion
high to low concentration (i.e. gut lumen to blood)
active transport
drugs moved across gut wall by transporter proteins
normally used for nutrients from food
disintegration
solid dosage form breaks into smaller pieces in GI tract
disolution
small pieces dissolve and release active ingredient
required for drug absorption
fastest to slowest rate of absorption
IV
SL
ODT
IR tablet
ER tablet
primary way IR formulations get destroyed in gut
hydrolysis
prevents drug degradation in stomach
enteric coating
micronized
drugs with very small particle diameters to increase dissolution rate by reducing particle diameter to increase surface area
solubility
how well drugs dissolve in GI fluids
typically lower for lipophilic
bioavailability
extent of drug absorption into systemic circulation
percentage of drug absorbed from extravascular compared to intravascular administration (oral vs IV)
high = >70% (levofloxacin, linezolid)
low = <10%
F x Dose = Cl x AUC
AUC
shows bioavailability
100 x (AUC extravasc/AUC intravasc) x (dose IV/dose extravasc)
dose of new dosage form
= amount absorbed from current dosage form / F of new dosage form
distribution
drug molecules move from systemic circulation to various tissues and organs
higher with high lipophilicity, low molecular weight, unionized status and low protein binding
albumin
main protein responsible for drug binding
unbound/free drug
exerts therapeutic/toxic effects
affect of low serum albumin and high protein-bound drug
more drug will be in unbound form than intended = higher therapeutic/toxic effects
highly protein bound compounds examples
phenytoin
calcium
need correction formulas for hypoalbuminemia
do not need corrections if “free phenytoin” or “ionized calcium” reported
calcium correction formula
serum Ca + [(4-albumin) x 0.8]
reports mg/dL
phenytoin correction formula
serum phenytoin / [(0.2 x albumin) + 0.1]
reports mcg/mL
volume of distribution
amount of drug in body / concentration of drug in plasma = dose / serum concentration
metabolism
drug is converted to facilitate elimination
primary sites for drug metabolism
gut
liver
first-pass metabolism
metabolism of drug before it gets.to systemic circulation
reduces bioavailability of oral formulations
Phase 1 reactions (oxidation, reduction, hydrolysis - such as adding hydroxyl group to make drug more hydrophilic) then Phase 2 reactions (conjugation)
drugs with high first-pass metabolism
lidocaine - cannot be given orally on IV
excretion
removal of drugs from body
pH affect on excretion
weak base - acidic urine increases excretion
weak acid - alkaline urine increases excretion
clearance
rate of elimination / drug concentration = (drug eliminated / how many hours to eliminate) / plasma concentration
efficiency of drug removal from body
most reliable measurement of drug’s bioavailability
AUC
first-order kinetics
constant percentage of drug is removed per unit of time
most drugs follow this
zero-order kinetics
a set of amount (mg) of drug removed per unit time
Michael-Mentin Kinetic /non-linear/saturable
enzymes for metabolism get saturated
follows first-order at very low concentration
at high concentrations, approach zero-order = inc dose causes disproportionate increase i
n drug concentration
drugs that follow Michael-Mentin Kinetics
phenytoin, theophylline, voriconazole
doses should be inc in small increments
eliminatio rate constant (ke)
fraction of drug liminated per unit of time
ke = Cl/Vd = how much of drug remaining is cleared per hour (ke = 0.1 hr means 10% of drug is cleared every hour
predicting drug concentration
C2 = C1 x e^(-ke x t)
half-life
time for drug concentration to dec by 50%
t 1/2 = 0.693/ke
steady state
where drug intake equals drug eliminatino
5 half-lives required to eliminate >95% or drug
loading dose
rapidly achieves therapeutic concentration of drug
= [(desired concentration) x Vd] / F
