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Pharmacokinetics Lect 2 Parameters, Vd

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alchemist04's version from 2016-06-29 22:01

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Vd(Amt of blood in the body)/(Plasma Conc. of Drug)
Dose (per Vd)Co * Vd ( where Co is the INITIAL PLASMA CONCENTRATION).
Plasma conc of drug isdose (mg) / volume (mL)
What is the unit for Dose?mg
What is the Unit for Vd?Unit is L , because it is based on Volume.
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Key points for Vd (1)High plasma binding protein drugs mostly binds to proteins and have few free drugs. Hence, have small volumes of distribution and small Vd.
Key points for Vd (2)The more lipid soluble (lipophilic) a drug the more readily it penetrates cell plasma membrane barriers and fat/adipose tissue. They have high Vd
Key points for Vd (3)Drug that binds to muscle and tissue are drugs that readily distributed out of plasma and into the tissue + muscle. Hence they have high Vd.
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T or F? Vd measurement is directly proportional to to the amount of free drug or the amount of unbounded fraction of drug in the plasmaTrue
Fu meansFree drugs ratio and equals (Plasma Concentration of unbound drug) / (Plasma Concentration of total drug)
T or F? The ratio of Fu has a limiting value of 0 - 1True
T or F? The lower the Fu, the more highly protein bound the drugTrue
T or F? The higher the Fu, the more free drugs, the more drug that is not bound to protein and less less protein bond drugTrue
T or F? If the Fu is high, the protein bound drug is lowTrue
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Fb is drug fraction bound to protein. It is mostly reported and must make conversion to Fu.
Fb conversionFu = 1 - Fb. Therefore, Fb = 1 - Fu. (1 = 100%, hence Fb is reported in percentage. E.g. if Fb is 75% then Fu = 1-0.75 = 0.25 or 25%)
What is the relationship btw Vd and Fu?Vd and Fu can be used to determine drug distribution and presence in the blood. This can be plotted as Vd (Y-axis) and Fu (X-axis). The graph shd be linear
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FutFraction Unbound in the tissue
FbtThe amt of drug that is bounded to the tissue. This is the only reported by the drug company, you will have to calculate the Fut. Since Fbt = 1 - Fut, then Fut = 1 - Fbt
Vd formula(Vp + Vt) (Fu/Fut) where Vp is the Plasma volume and is 3 mL; Vt is the apparent tissue Volume and is 38 mL
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Question Answer
Why is Vd a primary parameter for PK? (1)(1) it is an indication of the extent of distribution of the drug within the body
Why is Vd a primary parameter for PK? (2)(2) It is determined by the physiochemical properties of the drug and the physiological parameters of the patient
Why is Vd a primary parameter for PK? (3)(3) It depends on binding to both plasma proteins and tissue proteins
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