FTK 4: Pharmacokinetics Terms Flashcards
ADME?
A = absorption, BIOAVAILABILITY (how much of the drug reaches systemic circulation)
D = distribution, how much of the drug from the VASCULATURE gets into TARGET TISSUE
M = metabolism, the BIOTRANSFORMATION of a drug into metabolites, often done by the liver
E = elimination, REMOVAL of drug from the body, often done by the kidney
2 main routes of administration, 6 sub-categories for second one & drug administration
- INTRAVENOUS (IV)
- EXTRAVASCULAR
- IM
- PO
- RECTALLY
- INTRATHECAL
- TRANSDERMAL
- INHALATION
** MUST BE ABSORBED before we can do DISTRIBUTION, METABOLISM, & ELIMINATION OF DRUGS
volume of distribution
basic definition?
how is it measured?
formula?
what does it mean to have a SMALL Vd/what kinds of drugs have this?
what does it mean to have a LARGE Vd/what kinds of drugs have this?
= Parameter that describes how widely drug distributes within an APPARENT volume
Measured based on DOSE it was given and the plasma concentration we’re measuring
Vd = dose / plasma concentration
SMALL Vd = HIGH plasma concentration, drug is SEQUESTERED in plasma and doesn’t exit to tissues
HYDROPHILIC, ACIDIC, LARGE
LARGE Vd = LOW plasma concentration, drug DOES NOT STAY IN PLASMA LONG & goes to TARGET TISSUE
HYDROPHOBIC, BASIC, SMALL
half life, Vd, and Cl relationship & what it means
formula?
HIGHER HALF LIFE = HIGHER VD, LOWER CL
The longer a drug remains in plasma, the higher distribution it will participate in and lower amount of time for it to be cleared by the body (eliminated)
T1/2 = 0.693 x Vd (L) / Cl (body, L/min)
2 factors that affect drug ABSORPTION and 4 that affect drug ADME
ABSORPTION?
1. SURFACE AREA (GI/SKIN)
2. ENZYMES (acting locally PRIOR to absorption)
ADME?
1. LIPOPHILICITY = more lipophilic, higher Vd
2. IONIZATION = must have NO CHARGE to penetrate membranes
3. MOLECULAR WEIGHT = LARGER, higher Vd
4. TRANSPORTERS
Clearance (CL)
defines what 2 parameters?
total body clearance is..?
2 formulas?
defines BIOTRANSFORMATION & ELIMINATION
total body clearance = clearance from liver, kidney, and any other organ that performs clearance
formulas
1. CL = blood flow (L/min) x extraction ratio
2. extraction ratio = (concentration of drug IN - concentration of drug OUT) / concentration of drug IN
7 reasons we use pharmacokinetic (PK) models?
- to predict PLASMA concentration levels for ANY DOSE or DOSAGE REGIMEN given by the SAME ROUTE
- can we maintain therapeutic concentrations if we only change dose or dosage regimen? - calculate OPTIMUM DOSAGE REGIMEN for an INDIVIDUAL via THERAPEUTIC DOSAGE MONITORING
- estimate the possible ACCUMULATION of DRUGS or METABOLITES when REPEATED DOSING
- correlate DRUG CONCENTRATIONS with PHARMACOLOGIC or TOXICOLOGIC activity
- evaluate DIFFERENCES in BIOAVAILABILITY
- describe how changes in PHYSIOLOGY/DISEASE affects ADME
- explain DRUG INTERACTIONS
how do we make PK models?
EMPIRICALLY DETERMINED via IN VIVO ADMINISTRATION STUDIES
MOST substances follow what kind of PATTERN of elimination?
ONE-COMPARTMENT ELIMINATION MODEL
why are one-compartment elimination models considered linear?
because if you take the ln of both sides, it’s linear! OTHERWISE, EXPONENTIAL DECLINE
compartmental modeling
= definition
2 parts of graph?
= divides up the distribution of a drug THROUGHOUT THE BODY into COMPARTMENTS THAT ARE KINETICALLY IDENTICAL but NOT PHYSIOLOGICALLY IDENTICAL
what’s the BIG differentiation in non-compartmental modeling vs. compartmental?
non-compartmental modeling IGNORES THE ABSORPTION PHASE and takes a BEST FIT –> ONLY LOOKING THROUGH ELIMINATION PHASE
pros & cons of compartmental & non-compartmental modeling (2 each!)
COMPARTMENTAL
Pros?
1. Provides information about the COMPLETE PLASMA CONCENTRATION vs. TIME curve
2. Allows for SIMULATING DIFFERENT DOSES & DOSING INTERVALS but for ONE individual is best
Cons?
1. Variable profiles between subjects can make choosing a single model difficult or impossible
2. LOTS OF DATA POINTS NEEDED to enable the fitting process to succeed
NON-COMPARTMENTAL
Pros?
1. DOES NOT REQUIRE A CONSISTENT MODEL STRUCTURE
2. Requires FEWER data points
Cons?
1. CANNOT EXTRAPOLATE from ONE DOSE TO ANOTHER because we DO NOT HAVE THE COMPLETE CURVE –> CANNOT DO SIMULATIONS
2. Accuracy of pharmacokinetic parameters are COMPROMISED because ONLY FITTING TERMINAL (elimination) phase of the curve
If giving a drug to MULTIPLE ANIMALS and taking MANY BLOOD SAMPLES, what kind of modeling should we use?
NON-compartmental modeling
SINGLE bolus technique
formula?
mostly concerned with what parameter?
formula?
Dose (ug/kg) = Vd (L/kg) x Target Concentration of Plasma (ug/L)
mostly concerned with Vd (dose/target concentration of plasma)
