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Erythropoiesis and pharmacokinetics/...

Chapel, Sunny.

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Erythropoiesis and pharmacokinetics/pharmacodynamics of erythropoietin.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Erythropoiesis and pharmacokinetics/pharmacodynamics of erythropoietin./
Author:	Chapel, Sunny.
Description:	186 p.
Notes:	Source: Dissertation Abstracts International, Volume: 62-12, Section: B, page: 5663.
Contained By:	Dissertation Abstracts International62-12B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3034084
ISBN:	049347031X

Erythropoiesis and pharmacokinetics/pharmacodynamics of erythropoietin.
Chapel, Sunny.

Erythropoiesis and pharmacokinetics/pharmacodynamics of erythropoietin. - 186 p.

Source: Dissertation Abstracts International, Volume: 62-12, Section: B, page: 5663.

Thesis (Ph.D.)--The University of Iowa, 2001.

The pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of biotechnology-produced biopharmaceuticals is often more difficult than that of small molecules for several reasons including nonlinearity, changes in disposition depending on previous dosing history, and more complex elimination pathways. Recombinant erythropoietin (rhEPO), an important biotechnology-produced biopharmaceutical, is such an example. Sub-optimal rhEPO dosing may result from an incomplete understanding EPO's PK/PD.

ISBN: 049347031XSubjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Erythropoiesis and pharmacokinetics/pharmacodynamics of erythropoietin.
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020 $a 049347031X
035 $a (UnM)AAI3034084
035 $a AAI3034084
040 $a UnM $c UnM
100 1 $a Chapel, Sunny. $3 1929075
245 1 0 $a Erythropoiesis and pharmacokinetics/pharmacodynamics of erythropoietin.
300 $a 186 p.
500 $a Source: Dissertation Abstracts International, Volume: 62-12, Section: B, page: 5663.
500 $a Supervisor: Peter Veng-Pedersen.
502 $a Thesis (Ph.D.)--The University of Iowa, 2001.
520 $a The pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of biotechnology-produced biopharmaceuticals is often more difficult than that of small molecules for several reasons including nonlinearity, changes in disposition depending on previous dosing history, and more complex elimination pathways. Recombinant erythropoietin (rhEPO), an important biotechnology-produced biopharmaceutical, is such an example. Sub-optimal rhEPO dosing may result from an incomplete understanding EPO's PK/PD.
520 $a The aims of this work are to (1) test the hypothesis that the bone marrow is the major metabolic site of erythropoietin elimination, (2) evaluate nonlinearity and changes in EPO PK following bone marrow ablation and stimulation, (3) propose a new in vivo method (the Tracer Interaction Method (TIM)) for measuring nonlinearity, (4) propose an EPO PK/PD model, (5) compare PK/PD between newborns and adults using the sheep model, (6) propose a method of dealing with non-ideal tracers to study PK of endogenous compounds, and (7) propose a model to predict hemoglobin (Hb) levels in preterm infants for the first 4 weeks of life.
520 $a Our bone marrow ablation experiment in sheep suggested that the bone marrow accounts for 60--80% of EPO plasma clearance. The ablation reduced terminal half-life without changing volume of distribution and distribution half-life. EPO's nonlinear behavior in the normal dose range was manifested using TIM. Changes in EPO plasma clearance was clearly presented in phlebotomized sheep and an accompanying mechanistic model indicated that a positive feedback system may be involved in controlling the EPO receptor (EPOR) population. The proposed PK/PD models suggested that subcutaneous administration best mimics the body's natural release and full utilization of endogenous EPO in acute anemia. Newborns have larger volume of distribution and faster elimination than adults.
520 $a Suggestions for dosing improvement of EPO through PK/PD consideration are made. This work also may offer a model to mechanistically evaluate other protein drugs. The Hb prediction model in premature newborns developed in this work provides a kinetically-based strategy for choosing the time to start EPO therapy to reduce RBC transfusions.
590 $a School code: 0096.
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0572
690 $a 0419
710 2 0 $a The University of Iowa. $3 1017439
773 0 $t Dissertation Abstracts International $g 62-12B.
790 1 0 $a Veng-Pedersen, Peter, $e advisor
790 $a 0096
791 $a Ph.D.
792 $a 2001
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3034084