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Observations on the "Area under the curve" (AUC) for Omeprazole at different doses.

So I though I would plot a few theoretical curves to show the area concerned.

I suspect that the true effectiveness of PPIs is rather more complicated than "Area under the curve", especially at small frequent dosage levels where liver clearance is less dominant and blood serum concentration m ore constant. This should mean the lower dosage levels are even more effective.

First, the area corresponding to two 40mg doses of Omeprazole taken at 12 hourly intervals. Total per day = 80mg.

This assumes a linear rise from the point of taking a dose until peak concentration 3 hours later. Actual timing is variously quoted. It also assumes a liver clearance half time of 1 hour: 0.5 to 1 hour is commonly quoted. I have explained half life elsewhere and the half life effect means that plotting the concentration on a logarithmic scale, as here, concentration should fall in a straight line.

Secondly the same area but here the doses are 3 off 10mg. Same half life and time to peak as above. Liver clearance is still at the same rate: half life = 1 hour. Total per day = 30 mg

Thirdly the same curve but here dosage is 4 separate 5mg doses taken one every 6 hours. Total daily intake 20mg. See the afterword below!

What is astonishing on these 3 graphs is that the areas under these three curves are exactly the same!

It is quite clear that (if all the assumptions are valid) little and often reduces not only the total per day (hence the amount cleared by the liver) but the peak concentration.

Peak concentrations of the three regimes are

• 2 x 40mg gives a peak of 800
• 3 x 10mg gives a peak of 200
• 4 x 5mg gives a peak of 100

It is also very probable that any side effects are either due to work load on the liver or to peak blood serum concentration. By changing from two doses to 4 small doses peak levels should be reduced by a factor of 8! See another page explaining how I found out experimentally about minimum effective PPI dosage. See also the afterword below.

Assumptions made:

Time to peak is the same in each case (3 hours). Only part true as a smaller dose will probably be absorbed quicker. However whilst it is being absorbed, blood concentration will be less at smaller doses so liver clearance rate will be reduced. Practical departure from this assumption should affect all 3 curves similarly.

Blood serum level will rise steadily from ingestion to peak. As I have no way of testing the true shape of this curve, a straight (logarithmic) line is a convenience, but any error in this assumption should affect each curve in a similar manner.

Dominant serum level decay is by liver clearance - this is concentration dependant, with a half-life of 1 hour. Liver clearance in this way results in a straight line when plotted on a logarithmic scale.

The levels will not in practise show sharp peaks but will round off. I do not expect this will significantly alter the graphs.

The assertion that PPIs effectiveness is indeed proportional to the area under the curve... This is clearly an over-simplification as there is a blood plasma level at which the effect of the PPIs wears off. Small doses may well result in a blood level which is below the level for full control. In that case they will reduce acidity, but not completely. Whatever this level is, the it will define the bottom of the 'Area under the curve'! My experimental finding proved that 5mG was below this level!

Afterword

5mg doses clearly produce too low a blood level for complete inhibition and as far as I can make out, some degree tolerance to the drug was developing so that, whereas the drug had worked once, acid supression had decreased.

This is all personal surmise: a study on one specimen (myself) can never be 'scientific'. PPIs are said not to suffer from drug tilrance effects: I doubt that is true.

This also seems to prove the fallacy of the statement that effect is proportional to the area under the curve.

I am now taking three 10mg doses daily.

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