Understanding peak versus trough levels of meds

DEAR DR. ROACH: My doctor invariably prescribes four 200 mg Advils (ibuprofen), to be taken three times every 24 hours for a few days. I suspect this will create useful peaks, but also create unwanted troughs, compared to taking a smaller dose more frequently that results in the same aggregate dose every 24 hours.

My suspicion is that they are changing the optimal dosing schedule in order to achieve adherence. But I am a patient who is willing to do what works best. Whenever I tell them that I promise I will follow a better schedule if one exists, they don’t want to talk about it. Please sort out peaks versus troughs for me. There must be millions of people who would like to know this. — R.A.

ANSWER: I think most people are happy knowing that ibuprofen is safe to be taken the way it is recommended, but I hope some people will be interested in learning more about why we recommend dosing the way we do.

You are taking the maximum dose of ibuprofen: 2,400 mg a day. Most people do not need this high of a dose, as a lower dose is just as effective for pain relief, and the highest doses are used when the anti-inflammatory effect is needed.

Ibuprofen reaches its maximum level in the body about two hours after taking a tablet and will begin going down in the body afterward, due to the liver inactivating the medication. Every two hours or so, half of the dose is metabolized (naturally, this is called the half-life of a medicine). So, four hours after taking the dose, there’s about half the maximum; while at six hours, there is 1/4 of the maximum level. By the time you take another dose, only 1/8 of the medicine is left in the body, compared with the peak level two hours after taking.

Taking smaller doses more frequently will reduce the difference between the peak level and the lowest level, the trough, which occurs just before you take the next dose. So, if you took 600 mg four times a day (say, at 8 a.m., noon, 4 p.m., and 8 p.m.), the ibuprofen level in your body would not get below half the maximum during the day.

With some drugs, it is critically important to minimize the difference between peaks and troughs, but not so with ibuprofen, because it is effective at a very wide range of levels in the blood. It is not particularly toxic, even at the relatively high levels you get from taking 800 mg at one time. It is not completely safe, however, as ibuprofen can irritate the stomach lining, even causing ulcers, and can cause damage to the kidneys and other organs. Like all medicines, it should be used at the lowest effective dose for the shortest amount of time necessary.

Some medicines surprisingly do better with higher peaks and lower troughs. The antibiotic class called aminoglycosides, such as gentamycin, works better with longer intervals than we used to give in many instances. Many more bacteria are killed with high peaks, and a longer period below the toxic level protects the kidneys.

For ibuprofen, either 800 mg three times a day or 600 mg four times a day (or even 400 mg six times a day) is the same total dose, and all are likely to provide similar relief of pain and inflammation without a high risk of toxicity. But the shorter dosing intervals will probably have a small benefit in effectiveness.

Most people prefer the ease of administration of three times a day.

Finally, there are once-a-day prescription anti-inflammatories that have much longer half-lives.