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    Distribution of Drugs: Distribution Is Defined As The Reversible Transfer of Drugs Between Body Fluid Compartments

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    david5king-3119
    The document discusses the volume of distribution (Vd), which is the ratio between the amount of drug in the body and the drug's concentration in blood or plasma. A drug's Vd depends on factors like its physicochemical properties, degree of plasma protein binding, tissue storage, disease state, and body composition. Drugs that are lipid soluble, unionized, and highly bound to plasma proteins will have a lower Vd, while those that are sequestered in tissues can have a very high Vd. A drug's Vd can also be altered by conditions like congestive heart failure.

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    Distribution of Drugs: Distribution Is Defined As The Reversible Transfer of Drugs Between Body Fluid Compartments

    Uploaded by

    david5king-3119
    26 views9 pages
    The document discusses the volume of distribution (Vd), which is the ratio between the amount of drug in the body and the drug's concentration in blood or plasma. A drug's Vd depends on factors like its physicochemical properties, degree of plasma protein binding, tissue storage, disease state, and body composition. Drugs that are lipid soluble, unionized, and highly bound to plasma proteins will have a lower Vd, while those that are sequestered in tissues can have a very high Vd. A drug's Vd can also be altered by conditions like congestive heart failure.

    Original Description:

    Drug distribution in the body

    Original Title

    9.distribution

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    The document discusses the volume of distribution (Vd), which is the ratio between the amount of drug in the body and the drug's concentration in blood or plasma. A drug's Vd depends on factors like its physicochemical properties, degree of plasma protein binding, tissue storage, disease state, and body composition. Drugs that are lipid soluble, unionized, and highly bound to plasma proteins will have a lower Vd, while those that are sequestered in tissues can have a very high Vd. A drug's Vd can also be altered by conditions like congestive heart failure.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    26 views9 pages

    Distribution of Drugs: Distribution Is Defined As The Reversible Transfer of Drugs Between Body Fluid Compartments

    Uploaded by

    david5king-3119
    The document discusses the volume of distribution (Vd), which is the ratio between the amount of drug in the body and the drug's concentration in blood or plasma. A drug's Vd depends on factors like its physicochemical properties, degree of plasma protein binding, tissue storage, disease state, and body composition. Drugs that are lipid soluble, unionized, and highly bound to plasma proteins will have a lower Vd, while those that are sequestered in tissues can have a very high Vd. A drug's Vd can also be altered by conditions like congestive heart failure.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 9

    9.

    Distribution of Drugs
    Distribution is defined as the
    reversible transfer of drugs between
    body fluid compartments.
    Volume of Distribution

    • Volume of distribution (Vd) is the ratio between the amount


    of drug in body (dose given) and the concentration of the
    drug (C) measured in blood or plasma.
    • Vd = (amount of drug in body)/C where C is the
    concentration of drug in blood or plasma.
    • Vd as calculated is an apparent volume of distribution. For
    example:
    – Vd for digoxin is 440 L/70 kg (liters per 70 kg person)
    – Vd for chloroquine is 13,000 L/70 kg (liters per 70 kg person)
    – Such very large Vd would be consistent with very high tissue
    binding, leaving little free in plasma or blood
    • Vd is an apparent volume of distribution,
    since Vd is the volume needed to contain the
    amount of drug homogeneously at the
    concentration found in the blood, plasma, or
    plasma water.
    – Many drugs have a much higher concentration in
    extravascular compartments (therefore these
    drugs are NOT homogeneously distributed)
    Physical volumes (L./kg body weight) for some body
    compartments

    – Water
    • Total Body Water (0.5-0.7 L/kg) or about 35000 to
    49000 ml (70 kg individual)
    • Extracellular Water (0.2 L./kg)
    • Blood (0.08 L./kg);
    • Plasma (0.04 L./kg)
    – Fat
    • 0.2 - 0.35 L./kg
    – Bone
    • 0.07 L/kg
    • Semilogarithmic plot above illustrates extrapolation to time
    0 required to determine the volume of distribution;Vd =
    dose/Co- also note that the drug elimination halftime can be
    directly calculated from the graph. This graph applied for a
    single compartment model only. For multiple compartments
    which will appear as a. non-linear relationship extrapolation
    back to t = 0 must be performed for each compartment
    separately. (From Goodman Gilman, A, Rall T, Nies, A, Taylor P,
    eds Goodman and Gillman: The Pharmacological Basis of
    Therapeutics, 8th edn, Oxford: Pergamon, 1990)
    • Factors influencing the volume of distribution:
    – drug pKa
    – extent of drug-plasma protein binding
    – partition coefficient of the drug in fat (lipid solubility)
    – Vd may be affected by:
    • patient's gender
    • patient's age
    • patient's disease
    • patient's body composition
    – Example of a poorly lipid soluble agent with a Vd about equal to
    extracellular fluid volume: nondepolarizing neuromuscular
    blocking drugs.
    • 1.Physicochemical Properties of Drugs:
    • Lipid soluble and unionized form of drugs readily cross the cell
    membrane and are widely distributed e.g. lignocaine, propranolol, TCA
    • Drugs such as Heparin (Strongest Acid in the body) is confined only to
    intravascular compartments as it exists in ionized forms.
    • 2. Degree of Plasma Protein binding
    • Drugs that are highly bound to plasma proteins have a low volume of
    distribution
    • 3. Tissue storage
    • Certain drugs get sequesterated in some tissues. Such dugs have a large
    Vd e.g. Digoxin is sequesterated in heart, muscle, liver etc, and has Vd
    of 66L/Kg.
    • 4. Disease State:
    • The volume of distribution of drugs can be altered in
    certain diseases e.g. CHF, uremia etc. In CHF, the Vd of
    some drugs can increase due to increase in ECF or it
    could decrease due to decreased perfusion of tissues.
    • 5. Fat.
    • .Lean body mass ration… Highly lipid soluble drugs
    get distributed to the adipose tissues. If the ratio is
    high, the volume of distribution for such drugs will be
    higher and Fat acts as a reservoir for such drugs.

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