ArticleClinical pharmacokinetics2022
Real-Life Population Pharmacokinetics of Recombinant Factor XIII and Dosing Considerations for Preventing the Risk of Bleeding in Patients with FXIII Congenital Deficiency.
Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed, 5 citations in OpenAlex.
- Rare inherited coagulation disorders: no longer orphan and neglected.Research and practice in thrombosis and haemostasis · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveRecombinant factor XIII (rFXIII) at the recommended dosage of 35 IU/kg every 4 weeks is currently used for prophylaxis of bleeding in patients affected by FXIII deficiency. The aim of this study was to describe the population pharmacokinetics of rFXIII in patients with FXIII deficiency being treated with rFXIII in real-life and to assess, using Monte Carlo simulations, the attainment of defined FXIII concentration thresholds associated with prevention of the risk of bleeding over time.
methodsA nonlinear mixed-effects model approach was used for population analysis. Monte Carlo simulations were used to generate 10,000 FXIII concentration-time profiles associated with incremental doses of 25, 30, 35, 40, 45 and 50 IU/kg of rFXIII. The probability of target attainment (PTA) of FXIII concentrations at thresholds of > 0.05, > 0.10 and > 0.15 IU/mL were calculated weekly, from days 7 to 49.
resultsA total of 18 patients provided 99 FXIII concentrations; most patients (77.8%, 14/18) had severe FXIII deficiency. A two-compartment pharmacokinetic model with linear elimination from the central compartment best described rFXIII data. No covariates were associated with rFXIII disposition. Pharmacokinetic parameter estimates were 0.16 mL/h/kg for clearance, 57.35 mL/kg for volume of distribution at steady-state, and 11.72 days for elimination half-life. The standard 35 IU/kg dose resulted in PTAs of the pharmacodynamic thresholds of FXIII concentrations of > 0.05, > 0.10 and > 0.15 IU/mL at day 28 that were equal to 89.9%, 68.9% and 47.8%, respectively.
conclusionsIntensive FXIII monitoring from day 14, and/or shortening the dosing interval between rFXIII administrations, should be considered to minimise the risk of bleeding.
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.