Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 81, Issue 6, Pages 873-879Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.clpt.6100165
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL046925] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R21GM057367] Funding Source: NIH RePORTER
- NCRR NIH HHS [M01-RR-59] Funding Source: Medline
- NHLBI NIH HHS [P01 HL46925, P01 HL046925-11, P01 HL046925] Funding Source: Medline
- NIGMS NIH HHS [R21 GM57367] Funding Source: Medline
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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.
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