"Keep a watch also on the faults of the patients, which often make them lie about the taking of things prescribed", warned the father of medicine, Hippocrates, 2500 years ago. In the 1980s, Dr. C. Everett Koop, probably the best-known United States surgeon-general, famously summarised: "Drugs don't work in patients who don't take them."
Not much has changed. Studies indicate that up to 50 percent do not take their medicine - some forget, others deny the need for it. Still others take the wrong medication at the wrong time, or the wrong dose. At best, it invalidates patient care. At worst, it endangers their lives. It is an intractable problem that has existed as long as medical practice.
But perhaps not for much longer. IntelliDrug, a project funded by the European Commission, has developed a system - the prosthetic tooth - that delivers controlled drug doses at appropriate intervals, keeping the dose delivered within the exact therapeutic window. Better yet, it is easy to maintain and requires no invasive procedure.
"The oral cavity is very accessible, so the device can be easily installed, refilled or have its batteries replaced", stated Dr. Ben Z. Beiski, IntelliDrug co-inventor and project manager. "But passing the drug through the buccal - cheek - tissue also means much greater bioavailability."
Bioavailability refers to the body's capacity to absorb a substance. "Our evolution has designed us so that the body rejects or impedes alien substances and large, unusual molecules", stated Dr. Beiski. Molecules like those, typically, that make up many modern drugs.
The upshot is that most drugs suffer from the first-pass effect. Between stomach acid, the gastro-intestinal tract and, finally, the liver much - or even all - of a given dose is eliminated before it hits the bloodstream, where it does its work. "That's why we need intravenous injections, to avoid the first-pass effect", explained Dr. Beiski.
But IntelliDrug delivers the dose to the buccal tissue, on the inside of the cheek, where the body absorbs drug doses much more easily. Doses can be smaller and take effect quicker.
Here is how it works. The micro-system contains a reservoir and release mechanism; a programmable circuit, micro-sensors, an infrared sensor, micro-actuators and batteries. All housed in a tiny package. The circuit acts like a miniscule computer, releasing the dose required at the right time.
Ultimately, the batteries should last three months. Refilling the reservoir would vary, depending on the type of drug and dosage, but could range from every week to every month. In a later system, the team hopes to use radio-frequency identification (RFID) and later GSM telephony to communicate with the system. It is a demonstration of the power of multi-disciplinary co-operation between several scientific disciplines like micro-systems, micro-fluidics, dentistry, and pharmacy.
So far, the device has been tested successfully on pigs, which have similar oral characteristics. In November 2007, IntelliDrug enters human trials with twelve volunteers following naltrexone therapy, a heroin addiction treatment. If trials go well, IntelliDrug could be on the market in three years.
If successful, it could revolutionise treatment. The device can be applied to any drug, and Dr. Beiski sees applications for hypertensive patients to combat morning increases in blood pressure. Chronic pain, diabetics and Alzheimer's patients could benefit, too, making it an attractive system for patients and doctors.
For pharmaceutical companies, it is even more attractive, offering the equivalent of patent protection for generic drugs using the system. The combination would be protected by IntelliDrug intellectual property. But perhaps most important of all, it will mean, finally, an end to the 2500 year-old patient compliance conundrum.
More information is available at the IntelliDrug project website.