Intro Biopharmaceutics Flashcards
What does Bioavailability refer to?
Amount of drug that goes into the
-BLOOD
-TISSUES
Steps required for Absorption:
Disintegration -> Dissolution -> only when in solution it can be absorbed
How can bioavailability be measured?
-Pharmacokinetic profile: periodically take blood samples and measure the concentration of the blood -> curve
-Metric: Cmax, Tmax (time associated with Cmax),
AUC (area under the curve)
MEC (minimum effective concentration), MTC (maximal tolerance concentration) -> gap between MEC and MTC = therapeutic window
-time above MEC: Duration of effect: how much time the drug spends being therapeutically active
What does the fall of the concentration in the pharmacokinetic curve indicate?
-Metabolization of the drug
-Distribution into the tissues
-Elimination
What is happening at the top of the pharmacokinetic curve?
Absorption and Elimination is approximately equal
Recognize the rate process in the curve:
First order: the rate of absorption or elimination changes with the amount of concentration (high concentration -> high rate, decrease in concentration leads to decrease in the rate)
Zero order: constant decrease in rate, regardless of concentration
What is the rate process in the absorption and elimination phase of an orally administered drug?
First order: bc the rate is proportional to the concentration of the drug present in the body -> and the concentration is changing over time (for absorption and elimination)
How is Bioavailability designated?
-determined by AUC
-designated as F
-IV has 100% -> F=1
-IV used to compare -> other routes expressed as a fraction of 100% -> f.e. 0.8 = 80%
What does Biopharmaceutics deal with?
What is the effect of:
-Dosage form (tablet, solution, disintegration step involved?)
-Physico-chemical properties (solubility, lipophilicity, ionization)
-route of administration (IV, oral)
-Physiological function (taken after a heavy meal, drug transport across the membrane, first-pass metabolism for oral route)
–> effect on BIOAVAILABILITY
ADME: Absorption, Dissolution, Metabolism, Elimination
Which administration routes have the fastest onset?
- IV
- Inhaler: lung has a large surface area compared to the drug -> fast absorption
- Solution -> no disintegration
- capsule -> only the shell has to disintegrate
- tablet -> disintegration needed
- topical creams, and ointments -> have to cross dead skin (stratum cornea)
If the pharmacokinetics of the same drug is so different, why are there different dosage forms available?
-f.e. capsule form of Albendazole has low absorption
-absorption is not needed bc it works in the gut and interferes with the glucose absorption of the worms
-neuromuscular junction blocker for worms -> worms paralyzed
What are rate-limiting steps in oral drug absorption?
The slowest process prior to Absorption is the rate-limiting one (Bottlenecks)
-vary with the drug
-f.e. a compressed tablet will take a long to disintegrate (bottleneck)
f.e. insoluble drugs -> Dissolution is the bottleneck
What is the function of a diluent?
-It bulks up the volume, f.e. you have 10mg of the drug and you want 100;
-works as a binder
-in the stomach, it adsorbs the water and breaks up the tablet = DISINTEGRANT
Ka (up), Tmax (down), AUC (up)
-Lactose
Dibasic calcium phosphate
Starch
Microcrystalline cellulose
What is the function of Lubricant?
-Lubricants prevent the granules to get stuck in the hopper or puncher and ensure uniform granules
-they are lipophilic and delay wetting and disintegration
Ka (down), Tmax (up), AUC (down)
-Magnesium stearate
Stearic acid
Hydrogenated vegetable oil
Talc
The function of coating agents:
-delays the disintegration of the dosage form and dissolution of the drug -> to pass the stomach
Ka (down), Tmax (up), AUC (down)
-Methylcellulose
Cellulose acetate phthalate (CAP)
