ArticleJournal of pharmacokinetics and pharmacodynamics2007
Pharmacodynamic analysis of time-variant cellular disposition: reticulocyte disposition changes in phlebotomized sheep.
Article in Journal of pharmacokinetics and pharmacodynamics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Models for the red blood cell lifespan.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- A semi-mechanistic red blood cell survival model provides some insight into red blood cell destruction mechanisms.Journal of pharmacokinetics and pharmacodynamics · 2013Article
- Lifespan based indirect response models.Journal of pharmacokinetics and pharmacodynamics · 2012Review
- Receptor-based dosing optimization of erythropoietin in juvenile sheep after phlebotomy.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
- Pharmacodynamic analysis of stress erythropoiesis: change in erythropoietin receptor pool size following double phlebotomies in sheep.Biopharmaceutics & drug disposition · 2011Article
- Erythropoietic response to endogenous erythropoietin in premature very low birth weight infants.The Journal of pharmacology and experimental therapeutics · 2010Article
- Quantitative analysis of mechanisms that govern red blood cell age structure and dynamics during anaemia.PLoS computational biology · 2009Article
- Pharmacodynamic modeling of the effect of changes in the environment on cellular lifespan and cellular response.Journal of pharmacokinetics and pharmacodynamics · 2008Article
- Basic pharmacodynamic models for agents that alter the lifespan distribution of natural cells.Journal of pharmacokinetics and pharmacodynamics · 2008Article
- Modeling time variant distributions of cellular lifespans: increases in circulating reticulocyte lifespans following double phlebotomies in sheep.Journal of pharmacokinetics and pharmacodynamics · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Most pharmacodynamic (PD) models of cellular response assume a time-invariant (i.e., constant) cellular disposition despite known changes in the disposition with time, such as the reticulocyte residence time in the systemic circulation during stress erythropoiesis. To account for changes in cellular disposition, a comprehensive PD model that involves endogenous erythropoietin (Epo), reticulocytes, and hemoglobin responses was developed in phlebotomized sheep that considers a time-variant reticulocyte residence time and allows for the simultaneous determination of changes in the cellular disposition and cellular production. Five sheep were phlebotomized to hemoglobin concentrations of approximately 4 g/dl. Epo concentrations, reticulocytes, and hemoglobin concentrations were frequently sampled for 5-7 days prior to and 25-30 days following the phlebotomy. Initial steady-state conditions were assumed and the time-variant reticulocyte residence time in the systemic circulation was semiparametrically represented using a constrained spline function. Hemoglobin production was modeled using a Hill function via an effect site compartment. The initial steady state reticulocyte residence time in the systemic circulation was estimated as 0.477 (0.100) (mean (SD)) days, which maximally increased 2.01- to 2.64-fold higher than the initial steady-state residence time 5.95 (0.899) days post-phlebotomy (P < 0.01). On average, the residence time returned to steady-state values 15.4 (2.36) days post-phlebotomy, which was not significantly different from the initial steady-state value (P > 0.05). The baseline hemoglobin production rate was estimated at 0.0929 (0.0472) g/kg/day and the maximum production rate under stress phlebotomy was estimated at 0.504 (0.0422) g/kg/day. These data indicate that endogenously released Epo under acute anemic conditions can increase hemoglobin production approximately 5-fold. The determined increase in reticulocyte residence time produced under stress erythropoiesis is similar to the commonly reported 2- to 3-fold increase observed in human patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.