Distribution Flashcards
1
Q
Distribution
A
- Reversible transfer of drug between one location to another within the body.
- Depends on the rate of deliver to tissue, tissue permeability, drug bound to blood/tissue components
2
Q
Perfusion Rate Limitation
A
- Prevails when the tissue membranes essentially no barrier to distribution
- Highly lipophilic or very small molecules follow this rate
3
Q
Tissue Perfusion
A
- Varies considerably
- Well perfused tissues tend to take up drug rapidly
- Blood distribution: 14% brain, 27% liver, 22% kidneys, 15% muscle (when inactive), etc.
4
Q
Diffusion Rate Limitation
A
- Likely to occur with polar molecules diffusing across relatively impermeable membrane (BBB)
- Transfer is dependent on pKa, nature of drug, membrane
- Takes longer to achieve equilibrium
5
Q
Volumes of Distribution
A
- Relates a measured drug concentration to total amount in body
- Vd = Amount/Concentration = L
- Represents volume that must be considered when estimating the amount of drug in the body from drug concentration found in sampling compartment
- In general, drug reaches equilibrium rapidly
- Individual tissues may contain different concentrations due to differing affinities for drug
- Because of differences, Vd has NO true physiological meaning, so the term apparent volume of distribution is used which could be smaller, equal to, or larger than body mass
- Represents the result of dynamic drug distribution
6
Q
Physiological Volume
A
- Weight (kg) / Water displaced (L)
- Total body water = 64%
- Intracellular Fluid = 33%
- Extracellular Fluid = 27%
- Plasma = 4%
7
Q
Why do different drugs have different volumes? (5)
A
- Plasma protein binding (Increases, small Vd)
- Tissue protein binding (increases, larger Vd)
- Lipid solubility (Increases, larger Vd)
- Ionization (Increases, smaller Vd)
- Membrane Permeability (Increases, larger Vd)
8
Q
Is Vd small or large if drug is contained in vascular region?
A
Small
9
Q
Is Vd small or large if drug is contained in tissues?
A
Large
10
Q
Vd Calculation
A
V = Dose/Co
- IV only
- one compartment only, simplistic approach
- May be overestimation
11
Q
Vd: Model-Independent Method
A
V = FDose / K * AUC0-INF
- AUC - trapezoidal method
- K - empirically found
12
Q
Vd: Body Weight
A
V = Weight (kg) X Percent
13
Q
Drug Protein Binding
A
- Only unbound drug diffuses across membranes
- Reversible and rapid
- Extent of binding is expressed as UNBOUND fraction
- Varies considerably between 0 & 1
14
Q
Fraction Unbound Equation
A
Fraction Unbound = Cu /Ct (Ct = Cu + Cb)
Cu - concentration unbound in plasma
Cb - concentration bound
Ct - total concentration
15
Q
Drug Protein Binding Depends on…. (4)
A
- Affinity constant (strength of binding)
- Molar concentration of drug
- Protein concentration
- Number of binding sites per protein
