Development of new pharmaceuticals
Every experimental drug that moves from preclinical research in animal models to human clinical trials undergoes multiple investigations to establish safety and efficacy. Much of the work investigates what happens, as a function of time, following a dose. Drug administration may be oral, parenteral, transdermal, or pulmonary, among other routes. Thousands of blood samples are taken and then analyzed as a function of time after dose. Determining the concentration of the drugs and their metabolites, as well as their impact on endogenous substances, is important work. A lot goes on in a time-dependent fashion. Thus we examine many blood samples over time, collecting evidence that enables decisions about efficacy, safety, formulations design and frequency and route of administration. This varies with patient age, life style, other drugs simultaneously administered, genetics and disease. For example, kidney disease dramatically impacts circulating drug concentration over time.
The concentration of drugs and their metabolites, as a function of time, is referred to as pharmacokinetics (PK). It is likewise of great interest how endogenous substances respond to the dose (pharmacodynamics). These biomarkers may be indicative of efficacy or toxicity. With the Phlebot, it will be possible to collect accurate volumes of blood samples, at precise times, more frequently, safely and without waste. There is great potential for increasing the quality of the data and thus the quality of the decisions to be made
Sleep is essential, but we still don’t fully understand what happens when we do it, or even why we do it. Why do we have trouble sleeping? What happens to pharmacokinetics for a dose taken at bedtime, vs. breakfast? We are now well positioned to monitor many chemical parameters as well as the classical electrical signals (EEG) during various stages of sleep, but how can we do that if the subject is awakened during a blood draw? With the Phlebot, it is very possible to make biomarker and drug measurements during continuous sleep, as has already been demonstrated during animal studies. The results of such studies in humans are bound to be just as interesting.
Exercise physiology is an important topic. We have long been “wired” for heart rate, body temperature, respiration and electrocardiography during exercise, for example, on a treadmill. Painlessly and accurately collecting small blood volumes every 5 minutes (for example) is now practical. There is much to explore, including the impact of physical stress on pharmacokinetics and how individuals vary with respect to chemical indicators of stress such as cortisol and epinephrine.
Patients are placed in the ICU because their status is unstable and they are intensively monitored. We are all familiar with graphical displays monitoring heart rate, blood pressure, temperature, and respiration. Other than blood oxygenation, chemical measurements require a blood sample. Phlebotomy is accomplished manually, is labor intensive, wastes blood and subjects the patient to discomfort and infection risk. The time of blood collection is not programmable in advance. Accurate temporal information is mandatory when determining rates of change, a factor just as important for some blood components as it is for the price of a stock.
It is our contention at Phlebotics that each of these shortcomings can be overcome through the use of an automated system for blood collection. The technology has already been developed and proved its worth in research settings. Modern blood analysis technology requires much smaller blood volumes than in the past. NICU, PICU or ICU patients from whom serial blood collections are required need their blood. Why waste it? Reducing iatrogenic anemia is feasible while simultaneously acquiring more temporal data.
Over centuries, we've learned a lot about medicine by taking averages across many patients and using them to suggest what might work for any individual. There are 7 billion of us now, all measurably different in our biology, chemistry and physics. Until recently, we didn't have the tools to determine many of our distinguishing features. Several new clinical measurement tools have arrived. Not all of them are yet affordable for every circumstance, but every year more enter into routine use as they become cost effective, even for home use. Blood pressure monitors, glucose meters, pulse oximeters and digital thermometers are familiar examples.
When it comes to drugs, the concentration circulating in blood is more important than the amount dosed in a tablet. Too much and a drug may be dangerous. Too little and it may be ineffective. Why guess when we could measure? Patients differ in their ability to absorb the drug from the intestine, or the rate at which they break the drug down in the liver or excrete it through the kidney. Age matters. Diet and other medicines matter. There are many classes of drugs where the patient will benefit from the right drug, in the right dose, at the right time. Tools are becoming available to monitor more drugs, at lower concentrations, in smaller volumes of blood, more often and at lower cost. The Phlebot will be an enabler of these new technologies. We already know how beneficial this can be in critical areas like cancer drugs and immunosuppressant drugs following solid organ transplants. The jargon is "Therapeutic Drug Monitoring" (TDM) and we don't do enough of it. Our goal is to make it reliable, convenient and affordable.