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Lecture 9

Lecture 9 Drug Distribution

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Lecture 9 PCL201 Drug DistributionWhere do drugs distributeDrug distribution and potentially concentration will depend on blood flow and the physiochemical properties of the chemicaloLipid and water solubilityoIonizationoSize for hydrophilicoPlay a role in distribution ability to cross membranesoBlood flow to tissuesoCardiac OutputoTissue volumeWhat is volume of distributionVolume of Distribution ActualAnatomical volume accessible to the drugEg Charged compound ECFcant diffuse across membrane vs uncharger nonpolar compound can distribute to different areas TBWoECF vs TBW12L vs 42LVolume of Distribution ApparentThe hypothetical volume necessary to contain homogenous concentration in blood plasma or waterVd can be measure and calculated following IV injection of known compoundsLarge Vdnot concentrated low MW hydropholic lipid soluble access to more through diffusion through membranesIntermediate Vd concentrated in a smaller areaECF cant readily cross membranesSmall Vdquite concentratedDrug is concentrated in plasma compartmentVd provides information on where a drug will be found and where it wont be foundWhy is Vd importantKnowing the Vd of a drug allows us to calculate the dose required to achieve a desired plasma concentrationIn practiceWorks with respect to calculating drug concentrationsDoes not provide nformation on if the drug is effectiveHow can we calculate VdIv injection followed by measuring drug concentrations at specific time points Use semilog plot extrapolate to t0 remember to use antilogWhat information does Vd providesIncreased Vd not concentrated drug equilibrating to other places outside of plasma not found in plasma to a great extentVd not necessarily a measure of physical volume ratio of drug in compartments outside plasma relative to plasma allows for dose estimation
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