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Oral Administration : Dosing Regimen Strategy

Oral Administration : Dosing Regimen Strategy
11.3
Continuing on the dosing equation for oral admininstration. Now these two terms are equivalent if we assume same therapeutic concentration. Therefore, the equation is simplified to the second one. Therefore, the initial dose for the uremic patient is equal to the dose for the normal patient times a correction factor. Now, this equation is essentially the same as in the concentrate infusion except now we have one additional term, which is the ratio for the dosing interval Tau. So based on the dosing regimen equation if the dosing interval remains unchanged and the dose in renal failure should be reduced by a factor and that factor is the clearance ratio.
83.5
Now on the other hand, if the dose is to remain the same then the dosing interval should be prolonged and It should be prolonged by a factor and that factor is also the clearance ratio. However, if those dose and the dosing frequency are to be adjusted concurrently. Then the dosing rate is to be reduced. so this is the dosing rate in uremic the dosing rate in normal. And that’s the adjustment factor the clearance ratio However, this may be impractical to do to change dosing interval and the dose simultaneously. So to summarize the dosing regimen strategy in renal failure. Keep this same dosing interval, and reduce the dose, if the appropriate dosage of strength is available.
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Keep the same dose, prolong the dosing interval or change both. Adjust the dosing rate. Now the previous equation tell us to adjust dosing regimen based on clearance. Can we adjust dosing regimen based on K or half-life? because in the mission rate constant and half-life are more readily available than total clearance. so based on this equation, if volume distribution is the same for both the uremic patient and the patient with no more kidney function. Since clearance is the product of K times V so the equation to the left can be expended to the equation in the right. Now if we assume the same volume distribution.
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Then the volume distribution cancels out and that therefore we have dose in uremia is equal to dose in normal times a k ratio. And therefore we can use the K ratio to adjust dosing regimen. Assuming that the volume distribution is the same for renal failure patient and for patient with normal kidney function.

In this step, Prof. Lee introduces several equations based on assumptions that some parameters are unchanged.

First, if we assume that the therapeutic concentration (Css) and the bioavailability (F) are the same, the initial dose for patients in renal failure will be related to the clearance (Cl) and the dosing interval (tau).

Following that, if we assume the dosing interval remains unchanged, dose will be reduced by a factor of clearance ratio.

Besides, if dose and frequency are adjusted concurrently, dosing rate is to be reduced.

Finally, elimination rate constant and half-life are more readily available than total clearance. Assuming that the volume of distribution is the same for patients with renal failure and normal kidney function, we can use the K ratio to adjust dosing regimen.

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Pharmacokinetics: Drug Dosing in Renal Disease

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