Question

aill AT&T Wi-Fi令 7:33 AM a sepia2.unil.ch 100% plasma concentration must be reached more rapidly. A higher dose can then be administered on treatment initiation, to compensate for accumulation. Accumulation index (RAC): Index reflecting the extent of drug accumulation and determined by the ratio of plasma concentration at plateau over plasma concentration after the first dose. It depends only on the dosing interval with regard to the half-life of the ru Assessment The average steady state concentration can be assessed using the equation F. Dose T = dosing interval, hr The accumulation index (RAC) can be calculated by the following equation λ-elimination constant rate-CL/Vd Using the accumulation index the steady state concentration can be estimated by the equation Rate of accumulation to plateau: The amount of drug in the body rises on multiple dosing just as it does following a constant-rate IV infusion (see approach to the plateau depends solely on the drug's elimination half-life. The simulation for the antiepileptic drug phenobarbital in the the figure below illustrates this point. This drug has a half-life of 4 days (100 h) and is given at a dose of 100 mg ). That is, the
Can someone help break the accumulation index formula down for me with an example? I am working with a drug that has a 48 hour half life, and is supposed to be taken every 48 hours in a dosage of 75mg.

Answer 1

Phenobarbital is a long acting barbiturate that is used in humans for the treatment of its anticonvulsant and sedative-hypnotic properties and this is used for the treatment of all seizure disorders.

When the drug is administered following the intravenous infusion,the action usually occurs within 5 minutes and the maximum action can bee seen in the patients who is taking IV infusions are achieved within 30 minutes.

The half life of the drug phenobarbitol means the time required for the amount of drug in the body to be reduced by one-half or we can say that afer an half-life of phenobarbitol,the concentration of the drug in the body will be half of the starting dose(that means drug in the plasma or the amount in the body to be reduced by 50%).

Here the drug has a 48 hours half life,and is supposed to be taken every 48 hours in a dosage of 75mg.During the drug dosing interval there are some factors that affect the average concentration during the dosing interval are :

*Frequency of drug administration

*Elimination half life

*Rate of absorption

As a result of repeated dosing of the drug 75mg with a 48hour half life and is supposed to be taken every 48 hours ,the plasma concentrations reach higher concentrations during the repeated regimen due to the accumulation.

The accumulation ratio of a drug can be calculated by:

AR = ___1____________

1-e^-k*tau  

The denominator of the equation states that the proportion of the drug eliminated after one dosing intervals

Here we can see the drug is having 48 hours of half life and is administered for every 48 hours only

or we can break the accumulation index of the drug by using the AUC curve of the Trapezoidal rule and is by measuring the AUC on Day 1 to till last day of the admiministration,thus we can break the accumulation ratio of a drug.

We can break the accumulation ratio of a drug by using one of the these either method that is by calculating the drug t_1/2 (the time required for one half of the total amount of a particular substance in a biological system should be degraded) or by using AUC(Area under curve).

Any way the to know the accumulation index is very easy by using these two methods but the complex thing is that we should correctly calculate the dosing interval and the elimination rate constant,and the ratio can be controlled by changing the dosing frequency that should be be very careful