The Metabolism of Erythropoietin in Patients with Anemia Due to Deficient Erythropoiesis*

Rosse, Wendell F.; Waldmann, Thomas A.

doi:10.1172/jci105010

Cited by 35 publications

(13 citation statements)

References 16 publications

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“…In the present study, renal clearance of rHuEpo accounted for less than 3% of total body clearance and did not depend on renal function. These data are in close agreement with previous reports suggesting that in rats, dogs and humans the urinary excretion contributes only 4%-10% of the overall elimination rate of erythropoietin [11][12][13]. In view of this finding it seems likely that peripheral erythropoietin disposal occurs mainly through the liver and possiby through erythropoietic tissue.…”

Section: Discussionsupporting

confidence: 93%

“…This finding indicates that rHuEpo penetrates the extracellular space, even if the distribution volume of the hormone was found to be smaller than the latter. Confirmation of the substantial extravascular distribution space was also obtained in different animal species and in humans [6,[9][10][11][12]13,14]. The total body clearance values of rHuEpo obtained in this study were consistently low (0.0613-0.1203 ml/min per kg) and were not influenced by decreasing renal function.…”

Section: Discussionsupporting

confidence: 75%

“…The majority of previous studies on the pharmacokinetic profile of erythropoietin has been carried out with impure preparations using insensitive and highly variable bioassays for the determination of plasma disappearance of erythropoietin in different animal species and in humans [9][10][11][12]. In recent years the development of sensitive radioimmunoassays for erythropoietin has provided an important tool for studies on the pharmacokinetic behaviour of the hormone [7].…”

Section: Discussionmentioning

confidence: 99%

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Single-dose Pharmacokinetics of Recombinant Human Erythropoietin in Patients with Various Degrees of Renal Failure

Kindler¹,

Eckardt²,

Ehmer

et al. 1989

Nephrology Dialysis Transplantation

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Abstract. The pharmacokinetic profile of recombinant human erythropoietin (rHuEpo) was studied after a single intravenous dose of 150 U/kg in ten patients with various degrees of renal function: group I, creatinine clearance >80ml/min, n = 2; group II, creatinine clearance 10-50 ml/min, w = 6; group III, creatinine clearance <3ml/min (patients undergoing haemodialysis) n = 2. Erythropoietin concentrations in serum and urine samples obtained over 48 h were measured by RIA. rHuEpo was cleared from circulation in an exponential fashion, the half-life ranged from 6.5 to 12.7 h (mean 9.03 h) and was not different between the groups. The apparent volume of distribution varied from 0.041 to 0.099 I/kg (mean 0.070 I/kg) this corresponds to 1.5 times the plasma volume and was unrelated to kidney function. Renal clearance (groups I, II) accounted for less than 3% of total body clearance, both parameters were unaffected by decreasing renal function.These results indicate that, in accordance with animal data, the elimination of rHuEpo occurs mainly through non-renal mechanisms.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Single-dose Pharmacokinetics of Recombinant Human Erythropoietin in Patients with Various Degrees of Renal Failure

Kindler¹,

Eckardt²,

Ehmer

et al. 1989

Nephrology Dialysis Transplantation

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“…The biological half-life of erythropoietin in man is 25 hr (23), and it is even shorter in smaller animals (24,25).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype

Gabuzda¹,

Schuman²,

Silver³

et al. 1968

J. Clin. Invest.

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“…The regulation of Epo gene expression occurs mainly at the transcriptional level by DNA-dependent mRNA synthesis [16][17][18] and is controlled by an oxygen detection system that responds to changes in venous rather than arterial partial pressure of oxygen (PO 2 ) [19,20]. Clearance of Epo appears to be possible via three routes: excretion through the kidney [21], metabolism by the liver [22] or consumption by the erythron [23]. Epo is essential for the development of normal erythropoiesis, and underproduction of Epo results in anemia [16].…”

mentioning

confidence: 99%

cDNA cloning and expression of erythropoietin in the plateau zokor (Myospalax baileyi) from the Qinghai-Tibet Plateau

et al. 2012

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All organisms respond to variation in their environments and manage environmental stress through metabolic adjustments. The plateau zokor (Myospalax baileyi) is an endemic and keystone subterranean rodent species that inhabits the Qinghai-Tibet Plateau between 2800 and 4200 m above sea level. It is a hypoxic-tolerant mammal with a high ratio of oxygen utilization that enables it to cope with its harsh surroundings. To explore the molecular mechanism of altitude acclimatization of the plateau zokor, we cloned the zokor erythropoietin (Epo) gene and used real-time PCR to compare Epo mRNA levels in zokors inhabiting 16 different altitudes. The full-length zokor Epo open reading frame was 579 bp that encoded a precursor peptide of 192 amino acids with a signal peptide of 26 residues. The Epo gene of the plateau zokor was 81%-95% homologous to that of human, mouse, rat, root vole and the Golan Heights blind mole rat, with the highest homology (95%) to species of the genus Spalax. Epo mRNA was detected mainly in the zokor kidney and spleen among 8 selected tissues. The level of Epo mRNA increased in the liver and kidney with increases in altitude. The increase in the kidney was 5 times that in the liver. Remarkably, expression of Epo mRNA in the kidney of zokors living at the highest altitude (4268 m) was 12-fold higher than that of zokors living at the lowest (2492 m) altitude. These findings provide essential information for understanding the possible role of Epo in adaptation to hypoxia in the plateau zokor.

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The Metabolism of Erythropoietin in Patients with Anemia Due to Deficient Erythropoiesis*

Cited by 35 publications

References 16 publications

Single-dose Pharmacokinetics of Recombinant Human Erythropoietin in Patients with Various Degrees of Renal Failure

Single-dose Pharmacokinetics of Recombinant Human Erythropoietin in Patients with Various Degrees of Renal Failure

Erythropoietic kinetics in sheep studied by means of induced changes in hemoglobin phenotype

cDNA cloning and expression of erythropoietin in the plateau zokor (Myospalax baileyi) from the Qinghai-Tibet Plateau

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