Individualized Dosing Technique With Multiple Variables

Abstract

A method to quantify and correct for drug-drug interaction, physiologic change, diet, weight, genetic data and compliance on Warfarin dosing. The International Normalized Ratio (INR), a lab value used to follow Warfarin use, will fluctuate in an unpredictable manner due to factors other than the current Warfarin dose. The method mathematically describes these changes and eventually adjusts for these interacting factors through the use of logistic regression (LR) or multiple linear regression analysis. By anticipating changes in INR, Warfarin dosing can be adjusted resulting in patients having their INR be therapeutic range. The technique can be used in any field that requires a specific measured quantity, with variables that change and the need to correct for changes with a mathematical model.

1 . A method of determining a dose of anti-coagulant drug for a patient in need of anti-coagulant therapy to obtain a specific International Normalized Ratio comprising the steps of:
 a) conducting a patient intake by a health care professional comprising questions concerning health factors;
 current average daily dose of anti-coagulant drug in milligrams, 
 current international normalized ratio value, 
 patient's weight in kilograms, 
 patient's temperature, 
 number of episodes of fevers, 
 number of episodes of diarrhea, 
 amount and type of alcohol ingested, 
 current prescription drugs, including dosage, frequency and route of intake, 
 percent compliance of taking anti-coagulant drug, 
 kidney function, 
 liver function, 
 amount and type of Vitamin K containing food eaten, and any change in the intake of these foods, 
 number of bleeding episodes since last visit, and 
 number of clotting episodes since last visit; 
   b) recording the answers in step a) into a questionnaire to obtain values representing each category of question in step a);   c) entering the values from step b) into a mathematical model;   d) generating an equation of a line representing the relationship between the dose amount of the anti-coagulant drug and the INR in the patient;   e) using the equation generated in step d) to calculate the daily dose of the anti-coagulant drug to obtain the desired therapeutic INR score.   
     
     
         2 . The method of  claim 1 , further comprising in step a) the health care professional asking the patient at least one question of the health factors selected from the group consisting of:
 the patient's genetic information concerning anticoagulant therapy,   the patient's race,   the patient's age,   the patient's gender,   menopausal status of a female patient,   if patient is a vegetarian,   if patient is a vegan,   occurrence and duration of travel since last visit,   occurrences of trauma since last visit,   number of falls since last visit,   use of an illegal drug and if yes, the type, frequency and duration of illegal drug use,   intake of dietary supplements,   intake of over the counter medications,   intake of herbal, botanical and alternative medications,   type, frequency and duration of physical exercise,   any change altitude since previous visit,   any change in time zone since previous visit, and   any change in duration or frequency of sleep since previous visit   
     
     
         3 . The method of  claim 1 , wherein steps a) to e) are repeated during each subsequent visit by the patient. 
     
     
         4 . The method of  claim 1 , wherein the therapeutic INR score is between 2 and 3. 
     
     
         5 . The method of  claim 1 , wherein the mathematical model is selected from the group consisting of a logistic algorithm, multiple linear regression and logistic regression. 
     
     
         6 . The method of  claim 5 , wherein the mathematical model is logistic regression. 
     
     
         7 . The method of  claim 1 , wherein the mathematical model in step c) is a general model generated by data from multiple people. 
     
     
         8 . The method of  claim 1 , wherein the mathematical model in step c) is a model generated for a specific individual. 
     
     
         9 . The method of  claim 1 , wherein the mathematical model has a variable “z”, and wherein the z value for each health factor is generated by a logistic regression model. 
     
     
         10 . The method of  claim 9 , wherein the z value for each health factor generated by the logistic regression model is averaged between the population of patients answering the questionnaire to generate an averaged z value for that health factor and the averaged z value is used as the initial z value for a patient without an individual mathematical model. 
     
     
         11 . The method of  claim 1 , wherein the answers of the questionnaire from each visit by the patient are stored in a data base for that individual patient. 
     
     
         12 . The method of  claim 11 , wherein the data base is a secure database which is consistent with Health Insurance Portability and Accountability Act (HIPAA) and managed by a health care professional. 
     
     
         13 . The method of  claim 1 , wherein the answers are recorded in the questionnaire in digital form with “1” representing “yes” or “present” and “0” representing “no” or “absent”. 
     
     
         14 . The method of  claim 1 , wherein the anti-coagulant drug is selected from the group consisting of Warfarin, Coumadin, Jantoven, Marevan, Lawarin, Waran, Warfant and heparin. 
     
     
         15 . The method of  claim 1 , wherein the anti-coagulant drug is Warfarin. 
     
     
         16 . The method of  claim 1 , wherein the herbal medication is selected from the group consisting of Bromelains, Chamomile ( Matricaria recutita ), Coenzyme Q 10 , Cranberry products, Danshen, Dong quai, Echinacea ( Echinacea purpurea  and  Echinacea  spp.), Evening Primrose ( Oenothera biennis ), Feverfew ( Tanacetum parthenium ), Garlic ( Allium sativum ), Ginger ( Zingiber officinale ), Ginkgo ( Ginkgo biloba ), Ginseng ( Panax  spp.), Goldenseal ( Hydrastis canadensis ), Kava Kava ( Piper methysticum ), Milk Thistle ( Silybum marianum ), Saw Palmetto ( Serenoa repens ), St. John's Wort ( Hypericum perforatum ), and Valerian ( Valeriana officinalis ). 
     
     
         17 . The method of  claim 1 , wherein the prescription drugs and over the counter drugs are selected from the group consisting of antibiotics, aspirin, aspirin-containing products, nonsteroidal anti-inflammatory drugs, ibuprofen, naproxen, oral contraceptives, streptokinase, ticlopidine, and urokinase; and medications for cancer, cholesterol, colds, allergies, depression, diabetes, digestive problems, gout, heart disease, mental illness, pain, seizures, thyroid problems and tuberculosis. 
     
     
         18 . The method of  claim 1 , wherein steps a) to e) are repeated during each visit by the patient. 
     
     
         19 . A method of determining a dose of a drug for a patient in need of long-term therapy to obtain a specific laboratory test value comprising the steps of:
 a) conducting a patient intake by a health care professional comprising questions concerning health factors;
 current average daily dose of drug in milligrams, 
 current laboratory test value, 
 patient's weight in kilograms, 
 patient's temperature, 
 number of episodes of fevers, 
 number of episodes of diarrhea, 
 amount and type of alcohol ingested, 
 current medications, including dosage, frequency and route of intake, 
 percent compliance of taking drug, 
 kidney function, 
 liver function, 
 amount and type of food eaten, and any change in the intake of these foods, and 
 number of adverse episodes since last visit; 
   b) recording the answers in step a) into a questionnaire to obtain values representing each category of question in step a);   c) entering the values from step b) into a mathematical model;   d) generating an equation of a line representing the relationship between the dose amount of the drug and the laboratory test value;   e) using the equation generated in step d) to calculate the daily dose of the drug to obtain the desired laboratory test value.   
     
     
         20 . The method of  claim 19 , wherein the long-term therapy is selected from the group consisting of: hormone replacement therapy; radiation treatment, and chemotherapy. 
     
     
         21 . The method of  claim 19 , wherein the hormone replacement therapy comprises the replacement of a hormone selected from the group consisting of Melatonin (N-acetyl-5-methoxytryptamine) [MT]; Serotonin [5-HT]; Thyroxine (or tetraiodothyronine) [T4]; Triiodothyronine [T3]; levothyroxine; Epinephrine (or adrenaline) [EPI]; Norepinephrine (or noradrenaline) [NRE]; Dopamine (or prolactin inhibiting hormone) [DPM, PIH or DA]; Antimullerian hormone (or mullerian inhibiting factor or hormone) [AMH]; Adiponectin [Acrp30]; Adrenocorticotropic hormone (or corticotropin) [ACTH]; Angiotensinogen and angiotensin [AGT]; Antidiuretic hormone (or vasopressin, arginine vasopressin) [ADH]; Atrial-natriuretic peptide (or atriopeptin) [ANP]; Calcitonin [CT]; Cholecystokinin [CCK]; Corticotropin-releasing hormone [CRH]; Erythropoietin [EPO]; Follicle-stimulating hormone [FSH]; Gastrin [GRP]; Ghrelin; Glucagon [GCG]; Gonadotropin-releasing hormone [GnRH]; Growth hormone-releasing hormone [GHRH]; Human chorionic gonadotropin [hCG]; Human placental lactogen [HPL]; Growth hormone [GH or hGH]; Inhibin; Insulin [INS]; Insulin-like growth factor (or somatomedin) [IGF]; Leptin [LEP]; Luteinizing hormone [LH]; Melanocyte stimulating hormone [MSH or α-MSH]; Orexin; Oxytocin [OXT]; Parathyroid hormone [PTH]; Prolactin [PRL]; Relaxin [RLN]; Secretin [SCT]; Somatostatin [SRIF]; Thrombopoietin [TPO]; Thyroid-stimulating hormone (or thyrotropin) [TSH]; Thyrotropin-releasing hormone [TRH]; Cortisol; Aldosterone; Testosterone; Dehydroepiandrosterone [DHEA]; Androstenedione; Dihydrotestosterone [DHT]; Estradiol [E2]; Estrone; Estriol [E3]; Progesterone; Calcitriol (1,25-dihydroxyvitamin D3); Calcidiol (25-hydroxyvitamin D3); Prostaglandins [PG]; Leukotrienes [LT]; Prostacyclin [PGI2]; Thromboxane [TXA2]; Prolactin releasing hormone [PRH]; Lipotropin [PRH]; Brain natriuretic peptide [BNP]; Neuropeptide Y [NPY]; Histamine; Endothelin; Pancreatic polypeptide; Renin; Enkephalin; natural and synthetic endocrine drugs; and natural and synthetic endocrine analogues.