CoChat
Sign Up
Cited by 112Erythropoietin and Anemia TreatmentBiosimilars and Bioanalytical MethodsAntibiotics Pharmacokinetics and Efficacy

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects

Cheung, Wing K., Goon, Betty L., Guilfoyle, Mary C., Wacholtz, Mary C.·1998·Clinical Pharmacology & Therapeutics
DOI 10.1016/s0009-9236(98)90072-8
Open this paper in CoChat — free account

Abstract

OBJECTIVES: To understand the pharmacokinetic and pharmacodynamic properties of recombinant human erythropoietin (epoetin alfa) and to continue to optimize dosing regimens by determining whether administration of single high doses of epoetin alfa is as effective as repeated administration. METHODS: Epoetin alfa was administered as single subcutaneous doses of 300, 450, 600, 900, 1200, 1350, 1800, and 2400 IU/kg and in multiple subcutaneous dose regimens: 150 IU/kg 3 times a week for 4 weeks and 600 IU/kg once per week for 4 weeks in 2 open-label, randomized placebo-controlled studies in healthy volunteers. RESULTS: The absorption rate of epoetin alfa after subcutaneous administration was independent of dose, whereas clearance was dose-dependent in that it decreased with increasing dose. There was a linear relationship between response measured as percentage of reticulocytes area under the curve (AUC) and erythropoietin AUC for single doses up to 1800 IU/kg. Beyond the 1800 IU/kg dose, there was a saturation of response. The mean percentage of reticulocytes after single-dose regimens began to increase by days 3 to 4, reached their maximum at days 8 to 11, and returned to baseline values by day 22. In contrast, the mean percentage of reticulocytes after both multiple-dose regimens were maintained above baseline values through day 22 as both regimens stimulated modest but sustained increases in percentage of reticulocytes (1% to 2%). The mean percentage of reticulocytes AUC for 600 IU/kg epoetin alfa given once a week for 4 weeks was apparently greater than the mean percentage of reticulocytes AUC for 150 IU/kg 3 times a week for 4 weeks. Although daily oral iron supplementation was given, mean serum ferritin levels declined by approximately 75% through day 22 in subjects treated with multiple doses of epoetin alfa. CONCLUSIONS: These findings show that the pharmacologic response to epoetin alfa is a function of dose and dosing regimen. Repeated administration of epoetin alfa was more effective in stimulating a reticulocyte response than single-dose administration of the same total amount of epoetin alfa.

Integrity signals

Registry

Crossref · 10.1016/s0009-9236(98)90072-8

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In healthy volunteers and anemic patients with chronic kidney disease, a dose of recombinant erythropoietin of about 600 IU/kg led to maximum serum EPO levels of about 1,000 mIU/ml.

    “In healthy volunteers as well as anemic patients with chronic kidney disease, a dose of recombinant erythropoietin of about 600 IU/kg (which appears to be among the highest usually applied in clinical settings) led to maximum serum EPO levels of about 1,000 mIU/ml and an increase of the percentage of reticulocytes of about 2.39,40”

    From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [39]

  • A dose of recombinant erythropoietin of about 600 IU/kg appears to be among the highest usually applied in clinical settings.

    “(which appears to be among the highest usually applied in clinical settings)”

    From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [39]

  • In healthy volunteers and anemic patients with chronic kidney disease, a dose of recombinant erythropoietin of about 600 IU/kg led to an increase of the percentage of reticulocytes of about 2.

    “In healthy volunteers as well as anemic patients with chronic kidney disease, a dose of recombinant erythropoietin of about 600 IU/kg (which appears to be among the highest usually applied in clinical settings) led to maximum serum EPO levels of about 1,000 mIU/ml and an increase of the percentage of reticulocytes of about 2.39,40”

    From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [39]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Cheung, W. K., Goon, B. L., Guilfoyle, M. C., & Wacholtz, M. C.
Affiliations
Janssen Research & Development (United States) (US)
Corresponding author
Cheung, Wing K.
Venue
Clinical Pharmacology & Therapeutics
Publisher
Wiley
Published
1998-10
Volume
64
Issue
4
Pages
412-423
ISSN
  • 0009-9236 (ISSN-L)
  • 1532-6535
DOI
10.1016/s0009-9236(98)90072-8
OpenAlex
W2016474992
Cited by
112
References
21
Citations by year
2025: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 1 · 2013: 7 · 2012: 4
FWCI
2.80
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
  • Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
Keywords
epoetin alfa, recombinant human erythropoietin, pharmacokinetics, pharmacodynamics, subcutaneous administration, dosing regimen, repeated dosing, reticulocytes, dose-dependent clearance, dose saturation, serum ferritin, iron supplementation, anemia treatment, healthy volunteers, dose-response relationship
MeSH terms
Adult, Drug Administration Schedule, Erythropoietin, Ferritins, Hematocrit, Hemoglobins, Humans, Injections, Subcutaneous, Iron, Male, Recombinant Proteins, Reference Values, Reticulocyte Count, Area Under Curve

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review