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Change in Erythropoietin Pharmacokinetics Following Hematopoietic Transplantation
Author(s) -
Widness J A,
Schmidt R L,
Hohl R J,
Goldman F D,
AlHuniti N H,
Freise K J,
VengPedersen P
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100165
Subject(s) - erythropoietin , pharmacokinetics , medicine , bone marrow , transplantation , haematopoiesis , hematopoietic stem cell transplantation , pharmacology , stem cell , urology , biology , genetics
Pre‐clinical studies have demonstrated that bone marrow ablation has a profound effect in decreasing erythropoietin (EPO) elimination. The study's objective was to determine in humans if EPO pharmacokinetics (PKs) are perturbed following bone marrow ablation. EPO PK studies were performed in eight subjects, aged 4 to 61 years, undergoing fully myeloablative hematopoietic stem cell transplantation. Serial PK studies using intravenous injection of recombinant human EPO (92±2.0 U/kg) (mean±SEM) were carried out during four periods of altered marrow integrity: baseline pre‐ablation, post‐ablation pre‐transplant, early post‐transplant pre‐engraftment, and late post‐transplant full engraftment. Compared with baseline, post‐ablation pre‐transplant and early post‐transplant EPO PKs demonstrated declines in clearance increases in terminal elimination half‐life of 36 and 95%, respectively. Clearance and half‐life returned to baseline following full engraftment. The association of EPO elimination with decreased bone marrow activity in patients undergoing transplantation conclusively establishes the bone marrow as a key determinant of EPO elimination in humans. Clinical Pharmacology & Therapeutics (2007) 81 , 873–879. doi: 10.1038/sj.clpt.6100165 ; published online 11 April 2007