L35 - Drug Distribution 2 Flashcards
What is the therapeutic response and toxicity observed after uptake of a drug related to?
The body exposure to the drug
What 2 ways can you express the body exposure to the drug?
- drug conc (Cp) at a given time
- the area under the curve drug conc vs time (reflects the drug conc over a period of time)
What is the concentration of a drug in plasma a function of? (3)
- dose given
- extent of the drug distribution into tissues
- elimination kinetics
What is the extent of distribution for a drug given by?
Its apparent vol of distribution (V or Vd)
What does knowing the volume of distribution for a drug enable? (2)
- dose calculations
- estimation of the loading dose
What calculation can we use to deterime Vdistribution or Apparent volume?
Vdistribution = amount of drug in the body/conc of drug in plasma = apparent volume
What is V?
Apparent volume into which a drug dsitributes in the body once the equilibrium of distribution has been achieved
What are volume distribution and clearance used for as key parameters?
describe the fate of a drug in the body and its plasma concentration
What are some avg human body volume values (for 70kg subject)?
- blood = 5L (blood cells 2, plasma 3)
- extracellular water (plasma and interstitial water) = 15L
- intracellular water = 27L
- total body water = 42L
What is V used to do?
- relate the amount of drug in the body with the drug plasma concentration
- estimate the dose required to achieve a given conc (Crequired)
What is calculation for dose?
Dose = V x Crequired
What is the equilibrium eqn for volume distributino in relation to drug binding?
V = Vp + VT x (fu/fu.tissue)
What is the eqn for volume distribution in relation to the partition coefficient?
V = Vp + VT x P
What is the eqn for percentage of a drug present in plasms?
%plasma = (Vp x Cp/ V x Cp) x 100
= (Vp/V) x 100
What is the eqn for percentage of a drug present in tissues?
%tissues = (V x Cp - Vp x Cp / V x Cp) x 100
= (V-Vp/V) x 100
When does distribution process start?
Once drug reaches systemic ciruclation, immediately
When is the eq of distribution attained?
- binding event Cu = Ctissue
- partitioning events Cdrug.tissue = P x Cdrug.plasma
What may drug distribution be?
- perfusion (blood flow) rate limited
- permeability (diffusion) rate limited
What are examples of drugs that diffuse slowly across some membranes?
Polar drugs diffusing across the tighe and lipophilic membranes at the BBB
What are key facts about perfusion rate-limited distribution?
- changes in membrane permeability modify distribution // diseases that inc capillary permeability
- kinetics of distribution very dependent on the drug properties
What is the most frequent case in perfusion rate-limited distribution?
- when tissue membranes present no barrier to distribution
- access to tissues will be limited by blood flow (well perfused take up faster)
- changes in blood flow will modify distribution
What is the eqn for rate in and rate out?
Q x CA
Q x CV
What is the eqn for P (parition coefficient)?
P = CT/CV
What is the eqn for perfusion rate?
Q(CA-CV)
What is the eqn for rate of uptake?
Q(CA-CV)
What is the eqn for amount of drug in tissue?
VT x P X CV
What is the eqn for KT as first order>
KT = (Q/VT)/P
What is the eqn for tissue distribution half-life?
T1/2 = 0.693/KT
What does KT tell us?
How quickly the distributino process occur for a drug and tissue
- the larger KT
