Absorption and initial metabolism of ⁷⁵Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data

Abstract

Selenomethionine (SeMet) is an important organic nutritional source of Se, but the uptake and metabolism of SeMet are poorly characterised in humans. Dynamic gamma camera images of the abdominal region were acquired from eight healthy young men after the ingestion of radioactive 75 Se-L-SeMet ( 75 Se-SeMet). Scanning started simultaneously to the ingestion of 75 Se-SeMet and lasted 120 min. We generated timeactivity curves from two-dimensional regions of interest in the stomach, small intestine and liver. During scanning, blood samples were collected at 10-min intervals to generate plasma time-activity curves. A four-compartment model, augmented with a delay between the liver and plasma, was fitted to individual participants' data. The mean rate constant for 75 Se-SeMet transport was 2·63 h -1 from the stomach to the small intestine, 13·2 h -1 from the small intestine to the liver, 0·261 h -1 from the liver to the plasma and 0·267 h -1 from the stomach to the plasma. The delay in the liver was 0·714 h. Gamma camera imaging provides data for use in compartmental modelling of 75 Se-SeMet absorption and metabolism in humans. In clinical settings, the obtained rate constants and the delay in the liver may be useful variables for quantifying reduced intestinal absorption capacity or liver function.Key words: Selenomethionine: 75 Se-L-selenomethionine: Absorption capacity: Metabolism: Gamma camera imaging: Compartmental modelling Selenomethionine (SeMet) is an important organic nutritional source of Se (1,2) . Absorption of various Se compounds occurs via different routes and mechanisms. Membrane transport of selenoamino acids, including SeMet, involves a specific suite of amino acid transporters (3) . The subsequent incorporation of dietary Se into selenoproteins occurs through a series of interconversions, of which many details remain unknown. Se metabolites are excreted in the urine and faeces and in exhaled air, mainly as selenosugars and methylated compounds (4) .The initial metabolism of Se in humans is poorly characterised. Estimates of Se absorption, whole-body retention and excretion have been made predominantly on whole-body counting (5) or the recovery of ingested tracers in the blood, urine and faeces (6) . Compartmental analyses of kinetic data from tracer studies have also been used to create a more integrated picture of whole-body Se utilisation in humans (7,8) . These studies characterised the long-term kinetics by the investigation of urine and faecal data collected over 12 d and blood samples drawn over 4 months. Through detailed mathematical modelling including several plasma pools, they were able to provide new insights into the long-run Se metabolism. However, because the study data only comprised hourly observations after dose administration, the initial Se kinetics could not be investigated and therefore still remained unclear. Our study tries to fill this gap and to provide deeper insight into the initial Se kinetics by focusing on frequent data collection within the first 2 h after a...

Invited review: Mineral absorption mechanisms, mineral interactions that affect acid–base and antioxidant status, and diet considerations to improve mineral status

“…An alternative possibility to release of free ions in the small intestine and use of ion-specific transporters in the apical membrane of enterocytes is that the mineral crosses the apical membrane or tight junctions while still complexed. This is the case for selenomethionine and selenocysteine, which serve as Se supplements (Große Ruse et al, 2015), and is suggested to be the case for AA-mineral complexes that are on the market, assuming they reach the small intestine intact.…”

Inference for Biomedical Data by Using Diffusion Models with Covariates and Mixed Effects

“…The estimation quality in terms of sample size and sampling frequency was investigated in a simulation study for a popular model in pharmacokinetics, which was motivated by a recent study (Große Ruse et al, 2015). It includes subject-specific covariate information and is linear in parameters and state.…”

“…The model under investigation provides a proof of concept of our main application of modelling electroencephalography measurements of epileptic patients, which will be done in the next section, but is also inspired from a study on selenomethionine metabolism in humans (Große Ruse et al, 2015). This multi-dimensional linear transfer model finds frequent applicability in pharmacokinetics.…”

“…Moreover, we exemplify the framework with covariates for affine mixed effects. Section 3 is devoted to a simulation study in an example of the linear model, which is a submodel of the model that is used for the electroencephalography data, and which is common in pharmacokinetics and is motivated by a recent study on selenium metabolism in humans (Große Ruse et al, 2015). Here, we study finite sample and discretization bias of the estimation procedure and properties regarding hypothesis testing, where we investigate the effect of a drug treatment (as encoded by a covariate with levels treatment and placebo).…”

Multivariate inhomogeneous diffusion models with covariates and mixed effects

“…More specifically, we consider a multidimensional Ornstein-Uhlenbeck model with one covariate having two levels (e.g., treatment and placebo). This type of model is common in, e.g., pharmacokinetics, and is motivated by a recent study on Selenium metabolism in humans (Große Ruse et al, 2015). Moreover, we perform hypothesis testing on the treatment effect and investigate the performance of the Wald test.…”