WEBVTT
Kind: captions
Language: en
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In dealing with dosing adjustment in renal failure.
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We need to be cognizant of the assumptions.
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First, the assumptions related to the patient.
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We assume that renal failure patient
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and the otherwise normal patient share the same
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therapeutic concentration, nonrenal clearance, volume distribution,
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absorption and receptor sensitivity.
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Assumptions related to the drug itself.
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Now for renal failure patient, and otherwise normal patient
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The drug follows the same kinetic order.
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Or the drugs clearance is proportional to the creatinine clearance.
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And that the drug has the same tissue uptake.
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The assumptions or this assumptions are generally valid.
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However, there are exceptions
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Therefore, a rational approach is to initiate the dosing regimen based on these absorptions
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followed by therapeutic drug monitoring and the so called "learn and adapt".
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That during the learn and adapt process it may involve corrections for these assumptions.
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Now to keep the assumptions at the minimum,
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use patient specific PK information if available.
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Now, let's look at the dosing regimen equation.
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Dosing regimen equations are derived based on IV infusion,
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or oral administration.
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Let's start with constant rate intravenous infusion.
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Now if we infused a drug
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at constant rate for greater than 5 half-lives.
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Then the drug would reach at steady state.
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At the steady state,
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the concentration is equal to
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the infusion rate over the clearance.
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Now if we assume same therapeutic concentration
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then, the equation is transformed into the second one
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which indicate that the infusion rate in uremic patient
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is equal to the uremic infusion rate in normal patient
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times the clearance ratio.
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Therefore, the correction factor is the clearance ratio.
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Again, here C is the steady-state concentration
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which is defined generally as the therapeutic concentration.
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R: is the infusion rate.
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Cl: is the total clearance.
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and N: denotes normal kidney function.
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U: denotes uremic.
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Now if derived to base on oral administration.
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By the same token if a drug is given orally on a chronic basis or on multiple dose basis
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then eventually the drug will reach at steady state concentration.
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At steady state, the rate of drug input is equal to the rate of drug output.
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Rate of drug input is a fraction of the dose divided by Tau dosing interval.
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The rate of output is clearance times steady state concentration.
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Sorry, I need to back up a little bit and that therefore the steady-state concentration
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or the average steady-state concentration is equal to F dose over clearance times Tau.
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Here again just quickly the definition or the denotation.
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F is bio-availability.
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D is a dose.
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Tau is the dosing interval.
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Cl is the total clearance.
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and the Css is the average steady-state concentration.