Methods and compositions for therapeutic drug monitoring and dosing by point-of-care pharmacokinetic

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DESCRIPTION (OCR text may contain errors)

Personalized medicine as it applies to tailoring treatment of an individual patient with therapeutic agents has a pharmacokinetics (PK) study component where drug dose is optimized to the patient and a pharmacodynamics (PD) component where the treatment modality is matched to the patient. The treatment modality requires the understanding of the mechanism of action and mechanism of resistance. The identification of PD biomarkers has been the focus of considerable research effort, as evidenced by the tremendous growth of prognostic, predictive, and/or diagnostic biomarkers. However, the PK component is often neglected. Incomplete understanding of PK is now hampering PD biomarker testing from reaching its full potential.

Therapeutic drug monitoring (TDM) has the potential to revolutionize therapeutics by improving delivery of the drug as well as allowing for the correct application of biomarker testing. It is widely believed that identification of a biomarker predictive of response would allow targeted treatment of only those who would respond and spare those who would not respond to treatment. However, no matter how sensitive a disease is to a drug, an individual with the disease will not respond if the individual does not receive enough of the drug. This is where TDM would be expected to complement and advance the current effort on biomarker discovery.

However, personalized dosing has been typically a hit or miss process. Physicians are only given a general guideline as to the dosing of the patients, with much of the dose adjustment left to subjective observations of the patients. The Physician's Desk Reference snmmariyps experimentally-determined reasonable drug dosage ranges found in the research literature. These ranges are broad and the same dose is specified for all patients. Scientific research and publications exploring dose adjustment are not geared toward matching dose to individual patients. Rather, they provide a broad range of dosages based on averaging of characteristics over an entire population at worst, or only a subset of patients at best.

Researches recognize the need for finding new methods of accounting for inter-individual differences in drug response. Research over the past few decades has identified numerous factors that influence the clinical effects of medication. Age, gender, ethnicity, weight, obesity, concomitant morbidity, diet, and drug-drug interaction have all been found to influence both the pharmacokinetics study and pharmacodynamics of drugs. The pediatric population, women, racial minorities, and the elderly often require different dosing schedule than their male Caucasian counterparts.

Because of the large number of potentially interacting variables affecting individual response to treatment, a physician faced with the task of minimizing side effects and maximizing drug performance currently must rely on trial and error to refine dosages prescribed for a given individual. Subjective and objective methods are used to identity adverse symptoms and to implement changes necessary during the course of treatment. A common method of monitoring is clinical observation, which involves individual counseling and close personal supervision by physicians, who observe physiological signs and symptoms of the disease. This method is error- prone, time consuming, expensive, highly subjective, and unduly increases the doctor-patient contact time. Furthermore, patients are at risk for unnecessary toxicity from exposure to high levels of drug, or for receiving suboptimal or ineffective levels of treatment from insufficient levels of drug.

Accordingly, there is a need for improved methods of dosing of individuals using by therapeutic drug monitoring.