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Skip to 0 minutes and 11 seconds Now that we have finished calculating digoxin loading dose. Let’s move on to digoxin maintenance dose. Maintenance dose is to be given by PO. Let’s assume that bioavailability is 0.7 and a half life is about on 100-hour for this patient And the normal half-life is about forty hour. And the based on this equation the oral maintenance dose is equal to the therapeutic concentration times clearance over F over the bioavailability. We know the therapeutic concentration is 1.30 gram per mL. Clearance is the product of K times V and the K is 0.693 divided by 100. Changing a unit today minus one that is 0.16 times the volume distribution which is 464 liters divided by bioavailability of drug 70%.

Skip to 1 minute and 24 seconds And that turned out to be 137.7 microgram per day. So we’ve run it up to under 50 microgram per day that is to give 100 microgram capsule or tablet plus 150 microgram capsule or tablet. Now we know this dose is in the right ballpark because the loading dose we calculated previously is about three four times the maintenance dose. Let’s look at another example carboplatin. Now the carboplatin dose is equal to area under the curve times clearance. Therefore, the carboplatin dose is the desired AUC times carboplatin clearance. And that AUC is defined by the oncologist And with your assistant to be in a range of 3 to 8 miligram per mL times minutes So the question becomes other estimate carboplatin clearance.

Skip to 2 minutes and 53 seconds For male is determined by this equation. And for female it is this equation. So as long as you know weight, age and the serum creatinine you would be able to estimate carboplatin clearance in male or female. And once you know the clearance and once you know that desired area under the curve then you will be able to calculate a dose for the unique patient. So summarizing the dosing regimen in renal failure. Use patients specific PK information if available. You can take a general approach. Knowing the fraction of the dose. Excreted and change and knowing the kidney function. You can use the Nomograph. You can use a Nomogram which is a chart.

Skip to 3 minutes and 58 seconds You can use specific formula such as the Jusko formula. And then followed by TDM therapeutic drug monitor. And then learn and adapt adjust dose.

Example 4 : Carboplatin

Continuing, Prof. Lee explains how to calculate the oral maintenance dose of digoxin and how to estimate Carboplatin clearance.

First, we can assume that the bioavailability of digoxin is 0.7, and the half-life is 100 hr. Secondly, we can derive the daily dose by the formula. Finally, we should round it up to 150 ug/d, which can be one 0.1 mg +one 0.05 mg.

For example 4, we know that Carboplatin dosage (mg) would be the product of desired AUC and carboplatin clearance. However, please notice the differences in the formula between males and females.

Ultimately, Prof. Lee summarizes useful tools for the estimation of the dosing regimen in renal failure, including patient’s specific PK information, general formula, nomograph, specific formula, and TDM.

If you have any questions about this part, please leave them below.

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This video is from the free online course:

Pharmacokinetics: Drug Dosing in Renal Disease

Taipei Medical University