Pharmacokinetic and pharmacodynamic modeling of erythropoietin administration

Abstract

The present invention relates to systems and methods for obtaining optimized EPO dosage regimens for a desired pharmacodynamic/pharmacokinetic response. The system includes choosing one or more EPO dosage regimens, then using a PK/PD model to determine the pharmacodynamic/pharmacokinetic profile of one or more EPO dosage regimens, and finally selecting one of the EPO dosage regimens for administration to achieve the desired pharmacodynamic/pharmacodynamic response based on the EPO profile.

We claim:  
     
         1 . A method for obtaining optimized EPO dosage regimens for a desired pharmacodynamic response in a patient comprising the steps of: 
 (a) choosing one or more EPO dosage regimens;    (b) using a pharmacokinetic/pharmacodynamic model to determine the pharmacodynamic profile of said one or more EPO dosage regimens; and    (c) selecting said one or more EPO dosage regimens that provide said desired pharmacodynamic response based on said pharmacodynamic profile.    
     
     
         2 . The method of  claim 1 , wherein said pharmacodynamic response comprises of one or more of the group consisting of reticulocyte number, RBC number, and hemoglobin level.  
     
     
         3 . The method of  claim 1 , wherein said patient is anemic.  
     
     
         4 . The method of  claim 3 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         5 . The method of  claim 4 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         6 . The method of  claim 4 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         7 . The method of  claim 4 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         8 . The method of  claim 4 , wherein said anemia comprises drug related anemia.  
     
     
         9 . The method of  claim 8 , wherein said drug include cisplatin and zidovudine.  
     
     
         10 . The method of  claim 1 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         11 . The method of  claim 1 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         12 . The method of  claim 1 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         13 . The method of  claim 1 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         14 . A method for obtaining optimized EPO dosage regimens for a desired pharmacodynamic response in a patient comprising the steps of: 
 (a) selecting one or more desired pharmacodynamic responses;    (b) using a pharmacokinetic/pharmacodynamic model to determine EPO dosage regimens that provides said desired one or more pharmacodynamic responses; and    (c) selecting the one or more EPO dosage regimens that provide said desired pharmacodynamic responses.    
     
     
         15 . The method of  claim 14 , wherein said pharmacodynamic response comprises of one or more of the group consisting of reticulocyte number, RBC number, and hemoglobin level.  
     
     
         16 . The method of  claim 14 , wherein said patient is anemic.  
     
     
         17 . The method of  claim 16 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         18 . The method of  claim 17 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         19 . The method of  claim 17 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         20 . The method of  claim 17 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         21 . The method of  claim 17 , wherein said anemia comprises drug related anemia.  
     
     
         22 . The method of  claim 21 , wherein said drug include cisplatin and zidovudine.  
     
     
         23 . The method of  claim 14 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         24 . The method of  claim 14 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         25 . The method of  claim 14 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         26 . The method of  claim 14 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         27 . A system for selecting an optimal EPO dosage regimens for a patient using a pharmacokinetic/pharmacodynamic model comprising: 
 (a) a processor that is controlled in accordance with a set of program instructions that determine the steps implemented by said pharmacokinetic/pharmacodynamic model;    (b) a memory coupled to said processor, said memory storing the set of program instructions and parameters used by said pharmacokinetic/pharmacodynamic model; and    (c) a user interface, coupled to said processor, said user interface enabling a user to input parameters used by said pharmacokinetic/pharmacodynamic model.    
     
     
         28 . The method of  claim 27 , wherein said pharmacodynamic response comprises of one or more of the group consisting of reticulocyte number, RBC number, and hemoglobin level.  
     
     
         29 . The method of  claim 27 , wherein said patient is anemic.  
     
     
         30 . The method of  claim 29 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         31 . The method of  claim 30 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         32 . The method of  claim 30 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         33 . The method of  claim 30 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         34 . The method of  claim 30 , wherein said anemia comprises drug related anemia.  
     
     
         35 . The method of  claim 34 , wherein said drug include cisplatin and zidovudine.  
     
     
         36 . The method of  claim 27 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         37 . The method of  claim 27 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         38 . The method of  claim 27 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         39 . The method of  claim 27 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         40 . A computer program for obtaining optimized EPO dosage regimens for a desired pharmacodynamic response in a patient comprising: 
 (a) computer code that describes a pharmacokinetic/pharmacodynamic model for EPO, said code providing for selection of one or more desired pharmacodynamic responses and the use of said pharmacokinetic/pharmacodynamic model to determine one or more EPO dosage regimens that provide said desired one or more pharmacodynamic responses; and    (b) computer readable medium that stores said computer code.    
     
     
         41 . The method of  claim 40 , wherein said pharmacodynamic response comprises of one or more of the group consisting of reticulocyte number, RBC number, and hemoglobin level.  
     
     
         42 . The method of  claim 40 , wherein said patient is anemic.  
     
     
         43 . The method of  claim 42 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         44 . The method of  claim 43 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         45 . The method of  claim 43 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         46 . The method of  claim 43 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         47 . The method of  claim 43 , wherein said anemia comprises drug related anemia.  
     
     
         48 . The method of  claim 47 , wherein said drug include cisplatin and zidovudine.  
     
     
         49 . The method of  claim 40 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         50 . The method of  claim 40 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         51 . The method of  claim 40 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         52 . The method of  claim 40 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         53 . A computer program for obtaining optimized EPO dosage regimens for a desired pharmacodynamic response in a patient comprising: 
 (a) computer code that describes a pharmacokinetic/pharmacodynamic model for EPO, said code providing for user selection of one or more EPO dosage regimens and the use of said pharmacokinetic/pharmacodynamic model to determine a pharmacodynamic response for said one or more rHuEPO dosage regimens; and    (b) computer readable medium that stores said computer code.    
     
     
         54 . The method of  claim 53 , wherein said pharmacodynamic response comprises of one or more of the group consisting of reticulocyte number, RBC number, and hemoglobin level.  
     
     
         55 . The method of  claim 53 , wherein said patient is anemic.  
     
     
         56 . The method of  claim 55 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         57 . The method of  claim 56 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         58 . The method of  claim 56 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         59 . The method of  claim 56 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         60 . The method of  claim 56 , wherein said anemia comprises drug related anemia.  
     
     
         61 . The method of  claim 60 , wherein said drug include cisplatin and zidovudine.  
     
     
         62 . The method of  claim 53 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         63 . The method of  claim 53 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         64 . The method of  claim 53 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         65 . The method of  claim 53 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         66 . A method for obtaining optimized EPO dosage regimens for a desired pharmacokinetic response in a patient comprising the steps of: 
 (a) choosing one or more EPO dosage regimens;    (b) using a pharmacokinetic/pharmacodynamic model to determine the pharmacokinetic profile of said one or more EPO dosage regimens; and    (c) selecting the one or more EPO dosage regimens that provide said desired pharmacokinetic response based on said pharmacokinetic profile.    
     
     
         67 . The method of  claim 66 , wherein said pharmacokinetic response comprises of one or more of the group consisting of serum EPO levels, bioavailablity, and threshold level.  
     
     
         68 . The method of  claim 66 , wherein said patient is anemic.  
     
     
         69 . The method of  claim 68 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         70 . The method of  claim 69 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         71 . The method of  claim 69 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         72 . The method of  claim 69 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         73 . The method of  claim 69 , wherein said anemia comprises drug related anemia.  
     
     
         74 . The method of  claim 73 , wherein said drug include cisplatin and zidovudine.  
     
     
         75 . The method of  claim 66 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         76 . The method of  claim 66 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         77 . The method of  claim 66 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         78 . The method of  claim 66 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         79 . A method for obtaining optimized EPO dosage regimens for a desired pharmacokinetic response in a patient comprising the steps of: 
 (a) selecting one or more desired pharmacokinetic responses;    (b) using a pharmacokinetic/pharmacodynamic model to determine EPO dosage regimens that provide said desired one or more pharmacokinetic responses; and    (c) selecting one or more EPO dosage regimens that provide said desired pharmacokinetic responses.    
     
     
         80 . The method of  claim 79 , wherein said pharmacokinetic response comprises of one or more of the group consisting of serum EPO levels, bioavailability, and threshold level.  
     
     
         81 . The method of  claim 79 , wherein said patient is anemic.  
     
     
         82 . The method of  claim 81 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         83 . The method of  claim 82 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         84 . The method of  claim 82 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         85 . The method of  claim 82 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         86 . The method of  claim 82 , wherein said anemia comprises drug related anemia.  
     
     
         87 . The method of  claim 86 , wherein said drug include cisplatin and zidovudine.  
     
     
         88 . The method of  claim 79 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         89 . The method of  claim 79 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         90 . The method of  claim 79 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         91 . The method of  claim 79 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         92 . A computer program for obtaining optimized EPO dosage regimens for a desired pharmacokinetic response in a patient comprising: 
 (a) computer code that describes a pharmacokinetic/pharmacodynamic model for EPO, said code providing for selection of one or more desired pharmacokinetic responses and the use of said pharmacokinetic/pharmacodynamic model to determine one or more EPO dosage regimens that provide said desired one or more pharmacokinetic responses; and    (b) computer readable medium that stores said computer code.    
     
     
         93 . The method of  claim 92 , wherein said pharmacokinetic response comprises of one or more of the group consisting of serum EPO levels, bioavailability, and threshold level.  
     
     
         94 . The method of  claim 92 , wherein said patient is anemic.  
     
     
         95 . The method of  claim 94 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         96 . The method of  claim 95 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         97 . The method of  claim 95 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         98 . The method of  claim 95 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         99 . The method of  claim 95 , wherein said anemia comprises drug related anemia.  
     
     
         100 . The method of  claim 99 , wherein said drug include cisplatin and zidovudine.  
     
     
         101 . The method of  claim 92 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         102 . The method of  claim 92 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         103 . The method of  claim 92 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         104 . The method of  claim 92 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         105 . A computer program for obtaining optimized EPO dosage regimens for a desired pharmacokinetic response in a patient comprising: 
 (a) computer code that describes a pharmacokinetic/pharmacodynamic model for EPO, said code providing for user selection of one or more EPO dosage regimens and the use of said pharmacokinetic/pharmacodynamic model to determine a pharmacokinetic response for said one or more EPO dosage regimens; and    (b) computer readable medium that stores said computer code.    
     
     
         106 . The method of  claim 105 , wherein said pharmacokinetic response comprises of one or more of the group consisting of serum EPO levels, bioavailability, and threshold level.  
     
     
         107 . The method of  claim 105 , wherein said patient is anemic.  
     
     
         108 . The method of  claim 107 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         109 . The method of  claim 108 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         110 . The method of  claim 108 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         111 . The method of  claim 108 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         112 . The method of  claim 108 , wherein said anemia comprises drug related anemia.  
     
     
         113 . The method of  claim 112 , wherein said drug include cisplatin and zidovudine.  
     
     
         114 . The method of  claim 105 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         115 . The method of  claim 105 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         116 . The method of  claim 105 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         117 . The method of  claim 105 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         118 . A method for creating a pharmacokinetic model for subcutaneous EPO administration in patients comprising the steps of: 
 (a) obtaining pharmacokinetic data from patients;    (b) choosing an equation based on said data; and    (c) fitting said pharmacokinetic data to said equation.    
     
     
         119 . A method for creating a pharmacodynamic model for subcutaneous EPO administration in patients comprising the steps of: 
 (a) normalizing serum EPO concentrations;    (b) obtaining pharmacodynamic data;    (c) choosing a pharmacodynamic model;    (d) obtaining equation based on said model; and    (e) fitting pharmacodynamic data to said equation.    
     
     
         120 . The method of  claim 118 , wherein said obtaining pharmacokinetic data comprises: 
 (a) normalizing serum EPO concentration values from said pharmacokinetic data; and    (b) creating serum EPO versus time profiles based on said normalized data.    
     
     
         121 . The method of  claim 120 , wherein said normalizing step comprises: 
 (a) obtaining baseline serum EPO concentration values from said pharmacokinetic data by averaging predose serum EPO concentration values at plurality of time points;    (b) obtaining serum EPO concentration values following subcutaneous EPO administration;    (c) obtaining normalized serum EPO concentration values by subtracting predose EPO concentration values from serum EPO concentration values; and    (d) calculating mean normalized serum EPO concentration values at each time point.    
     
     
         122 . The method of  claim 118 , wherein said pharmacokinetic equation comprises the Michaelis-Menten equation.  
     
     
         123 . The method of  claim 118 , wherein said fitting step comprises obtaining estimates of pharmacokinetic parameters utilizing least-squares by Maximum Likelihood method and extended least squares model.  
     
     
         124 . The method of  claim 123 , wherein said parameters are selected from the group consisting of Vmax, Km, Vd, Ka, Fr, τ (lower doses), and τ (higher dose).  
     
     
         125 . The method of  claim 123 , wherein said fitting step comprises utilizing ADAPT II software.  
     
     
         126 . A method for calculating the bioavailability of EPO following subcutaneous administration comprises the steps of: 
 (a) obtaining pharmacokinetic data;    (b) calculating AUC;    (c) normalizing AUC to dose; and    (d) deriving an equation to represent said bioavailability of EPO by performing a linear regression of said pharmacokinetic data.    
     
     
         127 . The method of  claim 119 , wherein said normalizing step comprises: 
 (a) obtaining baseline serum EPO concentration (C bs ) for each dose group by averaging predose serum EPO concentration values at plurality of time points for each dose group; and    (b) adjusting C bs  by adding C bs  to serum EPO concentration predicted by pharmacokinetic model wherein said adjusted Cbs may be used as a forcing function for pharmacodynamic analysis.    
     
     
         128 . The method of  claim 119 , wherein said obtaining pharmacodynamic data step comprises: 
 (a) determining mean predose precursor cell number;    (b) determining mean predose reticolucyte number;    (c) determining mean predose RBC number;    (d) determining mean predose hemoglobin concentration;    (e) obtaining mean reticulocyte versus time profiles according to EPO dose;    (f) obtaining mean RBC versus time profiles according to EPO dose; and    (g) obtaining mean hemoglobin versus time profiles according to EPO dose.    
     
     
         129 . The method of  claim 119 , wherein said pharmacodynamic model comprises a cell production and cell loss model.  
     
     
         130 . The method of  claim 119 , wherein said fitting step comprises obtaining parameters utilizing least squares by Maximum Likelihood method and extended least squares model.  
     
     
         131 . The method of  claim 130 , wherein said parameters comprise estimated parameters and fixed parameters.  
     
     
         132 . The method of  claim 131 , wherein said estimated parameters comprise Ks, SC 50 , and TP.  
     
     
         133 . The method of  claim 131 , wherein said fixed parameters comprise R L , RBC L , Hb, and threshold.  
     
     
         134 . The method of  claim 130 , wherein said fitting step comprises utilizing ADAPT II software.  
     
     
         135 . A method for predicting a pharmacodynamic response in a patient to subcutaneous EPO administration comprising the steps of: 
 (a) selecting EPO dose and dosage regimens; and    (b) determining said pharmacodynamic response based on said dose and dosage regimens.    
     
     
         136 . The method of  claim 135 , wherein said pharmacodynamic response comprises of one or more of the group consisting of reticulocyte number, RBC number, and hemoglobin level.  
     
     
         137 . The method of  claim 135 , wherein said patient is anemic.  
     
     
         138 . The method of  claim 137 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         139 . The method of  claim 138 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         140 . The method of  claim 138 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         141 . The method of  claim 138 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         142 . The method of  claim 138 , wherein said anemia comprises drug related anemia.  
     
     
         143 . The method of  claim 142 , wherein said drug include cisplatin and zidovudine.  
     
     
         144 . The method of  claim 135 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         145 . The method of  claim 135 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         146 . The method of  claim 135 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         147 . The method of  claim 135 , wherein said dosage regimens are subcutaneous dosage regimens.  
     
     
         148 . A method for administering EPO comprising the steps of: 
 choosing one or more EPO dosage regimens using a pharmacokinetic/pharmacodynamic model to determine the pharmacodynamic profile of said one or more EPO regimens;    selecting said EPO dosage regimens that provides a desired pharmacodynamic response based on said pharmacodynamic profile; and    administering said EPO dosage regimen to a patient.    
     
     
         149 . The method of  claim 148 , wherein said EPO dosing regimen comprises administering EPO once a week.  
     
     
         150 . The method of  claim 148 , wherein said EPO dosing regimen comprises administering EPO twice a week.  
     
     
         151 . The method of  claim 148 , wherein said patient is anemic.  
     
     
         152 . The method of  claim 151 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         153 . The method of  claim 151 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         154 . The method of  claim 151 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         155 . The method of  claim 151 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         156 . The method of  claim 151 , wherein said anemia comprises drug related anemia.  
     
     
         157 . The method of  claim 156 , wherein said drug is selected from the group consisting of cisplatin and zidovudine.  
     
     
         158 . The method of  claim 148 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         159 . The method of  claim 148 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         160 . The method of  claim 148 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         161 . The method of  claim 148 , wherein said EPO dosage regimens are administered subcutaneously.  
     
     
         162 . A method of administering EPO comprising the steps of: 
 selecting one or more desired pharmacodynamic responses;    using a pharmacokinetic/pharmacodynamic model to determine EPO dosage regimen that provides said desired one or more pharmacodynamic responses;    selecting said one ore more EPO dosage regimens that provides said desired pharmacodynamic responses; and    administering said selected EPO dosage regiment to a patient.    
     
     
         163 . The method of  claim 162 , wherein said EPO dosage regimen comprises administering EPO once a week.  
     
     
         164 . The method of  claim 162 , wherein said EPO dosage regiment comprises administering EPO once every weeks.  
     
     
         165 . The method of  claim 162 , wherein said pharmacodynamic responses are selected from the groups consisting of reticulocyte number, RBC number, and hemoglobin level.  
     
     
         166 . The method of  claim 162 , wherein said patient is anemic.  
     
     
         167 . The method of  claim 162 , wherein said anemia comprises EPO concentration related anemia.  
     
     
         168 . The method of  claim 162 , wherein said anemia comprises end-stage renal or renal failure related anemia.  
     
     
         169 . The method of  claim 162 , wherein said anemia comprises cancer chemotherapy related anemia.  
     
     
         170 . The method of  claim 162 , wherein said anemia comprises AIDS drug therapy related anemia.  
     
     
         171 . The method of  claim 162 , wherein said anemia comprises drug related anemia.  
     
     
         172 . The method of  claim 171 , wherein said drug is selected from the group consisting of cisplatin and zidovudine.  
     
     
         173 . The method of  claim 162 , wherein said patient is undergoing autologous transfusion prior to surgery.  
     
     
         174 . The method of  claim 162 , wherein said patient is recovering from allogenic bone marrow transplant.  
     
     
         175 . The method of  claim 162 , wherein said patient is afflicted with rheumatoid arthritis.  
     
     
         176 . The method of  claim 162 , wherein said EPO dosage regimens are administered subcutaneously.  
     
     
         177 . A method for administering EPO to a patient comprising the step of: 
 administering said EPO on a once-weekly basis.    
     
     
         178 . The method of  claim 177 , wherein said administering comprises a dose 40,000 IU of said EPO.  
     
     
         179 . A method for administering EPO to a patient comprising the step of: 
 administering said EPO on a once every two week basis.    
     
     
         180 . The method of  claim 179 , wherein said administering comprises a dose selected from the group consisting of 80,000 IU/kg, 100,000 IU/kg, and 120,000 IU/kg.  
     
     
         181 . A method for enhancing the production of mature red blood cells from young red blood cells in a patient comprising the step of: administering EPO to said patient so that said young red blood cells are induced to become mature red blood cells.  
     
     
         182 . A method for maintaining an enhanced level of red blood cells in a patient comprising the step of: 
 administering a first dose of EPO followed by a second dose of EPO to said patient, wherein said second dose of EPO is administered to said patient at a time after said first dose that coincides with the production of reticulocytes resulting from said first dose of EPO.    
     
     
         183 . The method of  claim 182 , wherein said second dose of EPO is administered to said patient between six and twelve days after said first dose.  
     
     
         184 . The method of  claim 182 , wherein said second dose of EPO is administered to said patient between six and ten days after said first dose.  
     
     
         185 . The method of  claim 182 , wherein said second dose of EPO is administered to said patient seven days after said first dose.  
     
     
         186 . A business method comprising the step of: 
 providing to a consumer an EPO dosing regimen that is a first dose of EPO followed by a second dose of EPO to a patient, wherein said second dose of EPO is administered to said patient at a time after said first dose that coincides with the production of reticulocytes resulting from said first dose of EPO.    
     
     
         187 . The method of  claim 186 , wherein said EPO dose regimen comprises dosing one time per week with an effective amount of EPO.  
     
     
         188 . The method of  claim 187 , wherein said effective amount of EPO comprises 40,000 IU/kg.  
     
     
         189 . The method of  claim 186 , wherein said EPO dose regimen comprises dosing once every two weeks with an effective amount of EPO.  
     
     
         190 . The method of  claim 189 , wherein said effective amount of EPO is selected from the group consisting of 80,000 IU/kg, 100,000 IU/kg, and 120,000 IU/kg.  
     
     
         191 . A business method comprising the step of: 
 providing to a patient an EPO dosing regimen that is a first dose of EPO followed by a second dose of EPO to a patient, wherein said second dose of EPO is administered to said patient at a time after said first dose that coincides with the production of reticulocytes resulting from said first dose of EPO.    
     
     
         192 . The method of  claim 191 , wherein said EPO dose regimen comprises dosing one time per week with an effective amount of EPO.  
     
     
         193 . The method of  claim 192 , wherein said effective amount of EPO comprises 40,000 IU/kg.  
     
     
         194 . The method of  claim 191 , wherein said EPO dose regimen comprises dosing once every two weeks with an effective amount of EPO.  
     
     
         195 . The method of  claim 194 , wherein said effective amount of EPO is selected from the group consisting of 80,000 IU/kg, 100,000 IU/kg, and 120,000 IU/kg.  
     
     
         196 . A business method comprising the step of: 
 providing a dosing regimen of EPO to a user or patient.    
     
     
         197 . The method of  claim 196 , wherein said dosing regimen is once weekly.  
     
     
         198 . The method of  claim 196 , wherein said dosing regimen is once every two weeks.  
     
     
         199 . The method of  claim 196  further comprising the step of: 
 providing EPO in conjunction with said providing a dosing regimen of EPO to a user or patient.  
 
     
     
         200 . The method of  claim 196 , wherein said providing step comprises selling.  
     
     
         201 . The method of  claim 199 , wherein said providing step comprises selling.  
     
     
         202 . The method of  claim 196 , wherein said providing step is performed through the use of a computer system.  
     
     
         203 . The method of  claim 199 , wherein said providing step is performed through the use of a computer system.