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PLASMA PROTEIN BINDING

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Introduction: It is binding of drug to plasma protein in blood component.  Binding of drugs to plasma proteins is reversible.  Various plasma protein to which drug binds includes Albumin, α1-Acid glycoprotein (orosomucoid), lipoprotein, globulins, etc.  Order of binding of drugs to various plasma proteins:  Albumin > α1-Acid glycoprotein (orosomucoid) > Lipoproteins > Globulins Such bound drug is both pharmacokinetically as well as pharmacodynamically inert i.e. a protein bound drug is neither metabolized nor excreted nor it  is pharmacologically active.  A bound drug is also restricted since it remains confined to a particular tissue for which it has greater affinity. Moreover, such bound drug because of its enormous size cannot undergo membrane transport & thus its half life is increased.  However this binding is rapidly reversible and non-specific – that is many drugs may bind to the same protein. Drug–plasma protein bindi...

RENAL CLEARANCE

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Definition:  It is the volume of blood from which the drug is totally removed in unit time through renal excretion.   Expressed as CL R   It has units : mL/min  Major Organ for Excretion of Drugs is the Kidney.   Functional Units are  Nephron  Bowman‘s Capsule  Proximal Tubule  Loop of Henle  Distal Tubule  Collecting Duct  EQUATION: CL R  = Rate of urinary excretion / Plasma drug concentration  Physiologically,   CL R  =  Rate of Filtration + Rate of Secretion - Rate of Reabsorption                                     Plasma drug concentration (C)  Normal values of:  Renal blood flow (RBF) = 1200 ml/min   Glomerular filtration rate (GFR) = 125 ml/min   Urine flow = 1.5 ml/min.  GFR is measured by exogeneous /endogenous markers like Inuli...

VOLUME OF DISTRIBUTION

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The volume of distribution (VD) , also known as apparent volume of distribution, is used to quantify the distribution of a medication between plasma and the rest of the body after oral or parenteral dosing.   It is defined as the volume in which the amount of drug would need to be uniformly distributed to produce the observed blood concentration.   Volume of distribution may be increased by renal failure (due to fluid retention) and liver failure (due to altered body fluid and plasma protein binding). Conversely it may be decreased in dehydration.  EQUATION:  The volume of distribution is given by the following equation:    Therefore the dose required to give a certain plasma concentration can be determined if the VD for that drug is known. The VD is not a physiologic value; it is more a reflection of how a drug will distribute throughout the body depending on several physicochemical properties, e.g. solubility, charge, size, etc. ...

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