Pharmacokinetics Flashcards
Define pharmacokintics
The study of how the body deals with the drug via ADME
Drug factors that cause inter-patient variability.
Drug factors: dosage form, physiochemical properties (polarity)
Patient physiology factors that cause patient variability.
Patient physiology: GI motility, Gastric emptying rate, disease state
Non-drug/patient physiology factors that cause patient variability.
Drug-drug/food interaction
What are the PK parameters?
F: bioavailability
Vd: apparent volume of distribution
CL: clearance
t1/2: half-life
Ke: elimination rate constant
t1/2 and Ke are secondary PK parameters
Decribe the concept of F.
F is a measure of the amount of drug available to systemic circulation over time after administration.
F = bioavailability
F = (AUCoral/AUCiv) x (Doseiv/Doseoral)
Drug is only F when it reaches the hepatic vein
How does a drug become bioavailable?
Oral administration
- Drug has to disintegrate & dissolve in bodily fluids
- Some drugs must survive acidity in the stomach & breakdown by bacteria
- Drug has to be lipophilic to diffuse across enterocytes via passive-transcellular diffusion
Describe how Vd affects drug.
How to calc Vd?
- Drugs differ wrt the extent of their distribution within the body
- Vd influence drug dose required
Vd = A/C0
A = amount of drug administered
C0 = drug conc in plasma at time 0h
What could low Vd suggest?
- Drug is bound to albumin proteins in the plasma, prolonging drug action.
because only unbound drug can bind to receptors and exert effects
What could high Vd suggest?
- Drug is bound to tissues (muscles & fats), circulating in adipose tissues -> slows drug elimination
- but concentration of drug in plasma will be low
What happens to the Vd of a drug in the presence of valporic acid?
- Valporic acid has high affinity to albumin
- Valporic acid will bind competitively with albumin
- Prevents binding of albumin with new drug
- More new drug available for systemic circulation, increase in its Vd
Factors affecting drug distribution.
- body size
- lipid solubility of drug
- protein/tissue binding
- disease state
disease state eg less bound to plasma proteins?
Describe CL.
How to calc CL?
Refers to either
- renal excretion rate: amount of drug removed by kidney/time
- renal CL: amount of blood cleared of drug via urine/time
- Deals with metabolism (cata/ana)
CL(R) = U x V/C
U = urinary drug conc
V = vol of urine produced/time
C = plasma drug conc
Describe the metabolic clearance of paracetamol.
Phase I: Paracetamol converted to toxic metabolite NAPQI by cytochrome P450. NAPQI undergoes phase II (conjugation w glutathione GSH) to form hypophilic metabolite excreted in urine.
If there is insufficient GSH, NAPQI accumulates and reacts with body cells –> poisoning/cell death
80% of paracetamol undergoes phase II reaction immediately to form sulphat conjugate and glucaronic acidconjugate. (Safe)
Describe elimination.
It is the transfer of drugs from the body to the external environment, the main mode of termination of drug effects.
