Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Pharmacokinetic and pharmacodynamic modeling of erythropoietin administration

a technology of erythropoietin and erythropoietin, which is applied in the field of pharmacokinetic and pharmacodynamic modeling of erythropoietin administration, can solve the problems of large loss of blood, inconclusive data, and reduced oxygen availability in the tissues, and achieve the effect of facilitating the maturation of young red cells

Inactive Publication Date: 2006-06-15
CHEUNG WING +3
View PDF6 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides methods for optimizing the dosage regimes of EPO for desired pharmacodynamic and pharmacokinetic responses in patients. These methods involve using a PK / PD model to determine the optimal EPO dosage regimen that will provide the desired response based on the patient's needs. The methods can be implemented using computer software or computer code. The invention also includes a business method for providing an EPO dosing regimen to patients, which involves a first dose of EPO followed by a second dose of EPO at a time point that coincides with the PD profile resulting from the first dose. The second dose is preferably administered to coincide with the reticulocyte profile, which facilitates the maturation of young red cells in the circulation into mature RBCs. Overall, the invention provides a more effective and personalized approach for administering EPO to patients to achieve the desired therapeutic response."

Problems solved by technology

The primary site for EPO synthesis in adult organisms is the kidney; although the liver and bone marrow have also been implicated, the data remains inconclusive.
The primary stimulus for increased EPO synthesis is tissue hypoxia, which results from decreased oxygen availability in the tissues.
Hypoxia can result from the loss of large amounts of blood, destruction of red blood cells by radiation, or exposure to high altitudes.
In addition, various forms of anemia cause hypoxia since red blood cells are responsible for oxygen transport in the body.
Until recently, the availability of EPO has been very limited.
Although the protein is present in human urine, excreted levels are too low to make this a practical source of EPO for therapeutic uses.
Presently, there are a number of disadvantages associated as the standard EPO dosage regimen administered to patients.
Moreover, the standard dosing regimens may not maximize the patient's physiological response; and standard dosing regimens may not be the most cost efficient.
Furthermore, there are a number of disadvantages associated with the route of EPO administration: regular intravenous administration is inconvenient for the patient; intravenous administration is impractical for individuals afflicted with certain conditions such as continuous ambulatory peritoneal dialysis and non-dialysis patients with restricted vascular access; the rapid dose delivery of rHuEPO via intravenous administration results in a lower bioavailability of rHuEPO for longer time periods and may not be as effective for stimulating production of RBC as desired.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Pharmacokinetic and pharmacodynamic modeling of erythropoietin administration
  • Pharmacokinetic and pharmacodynamic modeling of erythropoietin administration
  • Pharmacokinetic and pharmacodynamic modeling of erythropoietin administration

Examples

Experimental program
Comparison scheme
Effect test

example 1

Human Pharmacokinetics and Bioavailability for EPO

[0249] The following example of the present invention provides a summary of the PK / PD data that support a 40,000-IU q.w. dosing regimen. The data are derived from both the literature and four clinical studies conducted by RWJPRI, Raritan, N.J. Three studies were conducted under Investigational New Drug BB-IND-2318, and one study was conducted in the UK. A brief overview of the studies is given in FIG. 17.

[0250] The clinical pharmacokinetic studies included in this technical summary are described FIG. 18A-18D, and the pharmacokinetic data from these studies are summarized in FIG. 19. The analytical methods used for the determination of EPO concentration in serum are summarized, infra, and FIG. 20.

[0251] Clinical Study EPO-PHI-373 (FIG. 17) provides the data to support the 40,000 IU once weekly dosing regimen. Clinical Study EPO-PHI-370 (FIG. 17), which has a similar design as Clinical Study EPO-PHI-373.

[0252] In Clinical Study EPO...

example 2

Evaluation of EPO PK / PD Profile After

Administration of 150 IU / kg t.i.w. and 40,000 IU q.w.

[0323] In specific indications, such as cancer, subjects are treated with 150 IU / kg epoetin alfa t.i.w. Thus, it remains an important goal to-change the currently approved dosing schedule to a more convenient (ie., once per week or once every two weeks) dosing schedule and regimen. A less frequent administration will improve user acceptance and convenience.

[0324] The pharmacokinetic and pharmacodynamic properties of the multiple dosing regimen of epoetin alfa have been defined in the previous example (EPO-PHI-358 and EPO-PHI-359). The data suggest that 150 IU / kg t.i.w. and 600 IU / kg / week dosing regimens have similar pharmacodynamic responses (e.g., a rise in hemoglobin). Therefore, epoetin alfa can potentially be administered as a weekly per kilogram dose. Since 600 IU / kg is equivalent to 42,000 IU / kg for a 70-kg person, the present study was conducted to demonstrate that a fixed dosing reg...

example 3

Comparison of PK / PD Parameters after Administration of EPREX® and PROLEASE®

[0417]FIG. 62 is a schematic representation of the model for erythropoiesis stimulating effects of rHuEpo. This model was used to estimate the kinetic and dynamic parameters for rHuEpo responses after administration of 8 single doses of EPREX® as well as the kinetic parameters after single dose PROLEASE® administration.

Pharmacokinetics

[0418] The pharmacokinetics of 600 IU / kg / wk EPREX® administered for 4 weeks was simulated using parameters obtained from the simultaneous fitting of the eight single doses. Only the Tau and Fr values were estimated. For the INT-57 cancer regimen of 150 IU / kg / t.i.w, the F, Tau, and Vd values were fixed as indicated in FIG. 63 based on previous estimations from the earlier study (EPO-358 / 359). The pharmacokinetics for single dose PROLEASE® (2400 IU / kg) were estimated and these parameters were used to simulate the multiple dose regimen of 1800 IU / kg / month. The same sets of kinet...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
percent reticulocyte-timeaaaaaaaaaa
body weightsaaaaaaaaaa
body weightsaaaaaaaaaa
Login to View More

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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to provisional application Ser. No. 60 / 133,418, filed May 11, 1999, the contents of which are incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to systems and methods for obtaining optimized EPO dosage regimens for a desired pharmacodynamic / pharmacokinetic response. BACKGROUND OF THE INVENTION [0003] Erythropoietin (EPO) is the principal factor responsible for the regulation of red blood cell production during steady-state conditions and for accelerating recovery of red blood cell mass following hemorrhage. EPO is a glycoprotein hormone with a molecular mass of 30 KDa and is heavily glycosylated, which serves to protect the EPO molecule from rapid degradation in vivo. Serum EPO concentrations in humans normally range from 6 to 32 U / 1 (1), and the half-life (t1 / 2) of EPO is reported to range from 2 to 13 hours with a volume of distribution close to plasma volume....

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/18G06F19/00A61K38/00A61K31/282A61K31/7072A61K33/243A61K38/12A61K38/22A61M37/00A61P7/00A61P7/06A61P7/08A61P13/12A61P19/02A61P29/00A61P31/18A61P35/00A61P43/00G06Q10/00
CPCA61K38/1816A61K38/14A61K33/24A61K31/70A61K31/505A61K31/475A61K31/28A61K2300/00A61K38/00G16H50/50G16C20/30A61P13/12A61P19/02A61P29/00A61P31/18A61P35/00A61P43/00A61P7/00A61P7/06A61P7/08A61K33/243A61K38/22
Inventor CHEUNG, WINGGIBSON, DAVIDCOTE, CHRISTINEVERCAMMEN, ELS
Owner CHEUNG WING
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com