How the body reacts to drugs

All drugs, man-made and natural, are foreign substances to the body, by definition. The body has mechanisms to deactivate and eliminate foreign substances. Drug design and administration takes this into consideration.

Drugs often become less effective over time because the liver adjusts. More metabolizing enzymes in the liver form to combat the foreign substance drug. In the old days when drugs were often derived from plants they were harder on the body because in addition to the active substance, other plant chemicals were included and these were often mild poisons. Even if the active ingredient were purified, the quantity of the drug was large and massive enzyme reaction in the liver was produced. Modern drugs get around this bodily reaction by being much more potent. The old drugs required that about a gram be taken every day while dosages on new drugs are 100 to 1000 times lower.

The other major organ responsible for fighting foreign substance is the kidneys. Some drugs are excreted unchanged in the urine. The kidneys recognize acidic or alkaline materials and remove them. Fat-soluble substances have a longer residence time inside the body because they are removed from the bloodstream into fatty areas and slowly diffuse outward over time.

The composition of the pills.

The typical dosage of a statin drug is under 100 mg per day. Its different from different drugs and different patients – your doctor will tell you the best dosage for you. But the actual pill you swallow is much larger than 100 mg. That’s because the dosage of the active drug is so small. Most of what is in that pill is inactive filler: starches, oils, etc. Different manufacturers use different formulations. All statins on the market are in pill form. These drugs are not typically delivered by injection or skin patch. Further, unlike some slow release medicines, statin pills are not formulated to dissolve particularly slowly or over time. Slow release medicines are employed when the serum levels of the drug are important to control over time. This is not an important consideration in statin usage.

OTC vs. Prescription drugs

New drugs developed by pharmaceutical companies always start as prescription medications. Sometimes new herbal medicines on the market might go straight to over-the-counter status, but the big drug companies make drugs that are sold only by prescription. This is society’s way of limiting risk, institutionalizing prudence, and controlling access to what might be dangerous materials. Doctors explicitly control the dosages for the patients to reduce the risk of overdoses. After several years and many (millions?) of patients with experience using the new medicine, the regulatory authorities have enough information to decide whether to allow a drug to go OTC. Drugs that have the potential for abuse or where medical supervision is necessary are not approved for OTC sale.

Several popular drugs have gone this route. Think minoxidil (Rogaine) and Claritin. Insurance companies (including Medicare) benefit when drugs move to OTC status as they are generally cheaper and do not require an expensive doctor's visit. Large drug companies may also welcome OTC status as a way of managing their product lifecycle, especially when a drug is about to go off-patent. In Britain, simvastatin (Zocor) is now available “behind-the-counter” , although it should be noted that this is different from OTC in the United States as it allows a pharmacists to give advice to and interact with the patient.

In December 2007, an FDA advisory board considered a request from Merck to let Mevacor (lovastatin) go over the counter, but the board voted 10-2 against the proposal. Formal action by the FDA should happen in 2008. The UK allows direct purchase of simvastatin (Zocor) if the consumer is certified to be at risk for a heart attack, and the dosage is lower than the prescription strength.

Might statins go OTC in the future? It doesn’t appear likely now, mostly because of concerns about the effects of statins on liver function and because the dosage for different people varies so widely.