ADMET Flashcards
Disposition
-Distribution and elimination (Metabolism and Excretion)
ADMET
-Absorption
-disposition (Distribution and elimination (Metabolism and Excretion)
-Toxicity
elimination
-removal of drug via metabolism and excretion
Toxicity
result of exposure
Plasma vs Time curves
can determine each phase of ADMET
Pharmacokinetic view
dresser (person) vs drawers (organs)
Sampling sites (exposure)
-blood, plasma, serum
-urine
Sites of delivery
-arterial
-venous
-SC,IM
-pulmonary
-oral
Elimination site
-gut metabolism
-exhalation
-hepatic metabolism
-fecal excretion
-renal excretion
Drug distribution
-dependent on physiochemical properties
-lipophillic vs hydrophillic
Lipophilic drugs
-partition into fatty tissues
Hydrophillic drugs
-partition into tissues where endothelium is permissive
Pharmacokinetic Process
-defined by concentration vs time profiles
-compartments represent kinetically similar tissues
-reversible or irreversible
-linear or nonlinear
-fast and slow processes tend to disappear
Differences in blood perfusion rates after drug distribution
-dictate organ distribution levels
Distribution Limitations
-perfusion rate
-permeability rate
-convection
-diffusion
Perfusion rate
-blood flow to tissues
Permeability rate
-membrane permeability
convection
-mechanism of transvascular transport
-pressure gradient
Diffusion
concentration gradient
Typical Plasma vs time curve
-increase to peak during absorption (Cmax, Tmax)
-decrease through the rest of the phases
AUC
area under curve
Tmax
time to reach maximum blood concentration
Cmax
maximum blood concentration of dosage form
Bioavailability
rate and extent of drug absorption
Absolute bioavailability
AUC of given dosge form compared to AUC of same dose injected intravenously
Relative bioavailability
AUC of given dosage form compared to arbitrary reference standard
Bioequivalence
does NOT mean the therapeutic effect of the two dosage froms are equivalent
Paracelsus
“everything is poison actually it’s just the dose”
Paraclesian theory
chemical may have no effect, beneficial effect or toxic effect
dose-response relationship
-most important factor in pharmacology and toxicology
Dose
-amount of chemical
-local concentration of chemical at response site
dose-receptor concentration
function of ADME
Absorption rate (Kabs) defined by
-drug properties
-excipient/drug composition
-physiological barriers between GI tract and systemic circulation
Absorption rate controlled by
-formulation parameters that are optimized to provide a Cmax and Tmax associated with safe and efficacious response = therapy is realized
Influences of efficacy and safety
-duration of drug plasma concentration in the therapeutic window (Cmax and T max)
-duration of chronic therapy
Potential Worsening of disease
Prolonged exposure to subtherapeutic doses or ineffective drugs
Therapeutic window
-concentration of drug between the minimum effective level and the minimum toxic level
MTC
minimum toxic level
MEC
minimum effective level
True (A) or False (B): BIOAVAILABILITY is the fraction of an
administered dose that reaches the systemic circulation
intact.
True
True (A) or False (B): Dosage forms are designed to convey
performance by balancing the composition of the excipients,
the drug’s physicochemical properties and to overcome the
physiological barriers required for a safe and efficacious
response.
True
True (A) or False (B): When blinding clinical trials, it is often
important to mask the ORGANOLEPTIC properties of the
comparator and the drug being tested. These senses include
sight, smell, taste, touch, and sound.
True
True (A) or False (B): The STOMACH has a significantly
increased surface area due to villi, folds of Keckring, and
microvilli.
FALSE, intestine
Which is NOT included in the acronym of ADMET?
Dissolution
True (a) or False (f): The microenvironmental pH at the membrane surface may
be different than the lumen based on the fact that the mucus and the glycocalyx
have buffering effects.
True
True (a) or False (b): Drug levels observed in the therapeutic window can be
governed in part by transporters and metabolism, based on the compound being
studied. Therefore, transporters and enzymes do not play an important role in
drug product performance.
FALSE
All of the following can reduce the bioavailability of an orally administered drug
EXCEPT:
a) Poor dissolution in the GI tract
b) Poor penetration of the blood-brain barrier Ans
c) Chemical degradation in the GI tract
d) Poor solubility in the GI fluids
e) Poor absorption across the GI mucosa
