Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system

<p>Abstract</p> <p>Background</p> <p>Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system.</p> <p>Methods</p> <p>A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4 × 4) giving a position defined by 5 coordinates (position: <b>x, y, z, and angle: θ, ϕ)</b>. Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state.</p> <p>Results</p> <p>Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min^-1vs. 10.53 min^-1) (p = 0.03).</p> <p>Conclusion</p> <p>MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.</p

The role of population PK-PD modelling in paediatric clinical research

Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK-PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK-PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK-PD parameters with the highest precision. Once a population PK-PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child