Population pharmacokinetic modelling of rupatadine solution in 6–11 year olds and optimisation of the experimental design in younger children

by Eva Santamaría, Javier Alejandro Estévez, Jordi Riba, Iñaki Izquierdo, Marta Valle

Aims

To optimise a pharmacokinetic (PK) study design of rupatadine for 2–5 year olds by using a population PK model developed with data from a study in 6–11 year olds. The design optimisation was driven by the need to avoid children's discomfort in the study.

Methods

PK data from 6–11 year olds with allergic rhinitis available from a previous study were used to construct a population PK model which we used in simulations to assess the dose to administer in a study in 2–5 year olds. In addition, an optimal design approach was used to determine the most appropriate number of sampling groups, sampling days, total samples and sampling times.

Results

A two-compartmental model with first-order absorption and elimination, with clearance dependent on weight adequately described the PK of rupatadine for 6–11 year olds. The dose selected for a trial in 2–5 year olds was 2.5 mg, as it provided a Cmax below the 3 ng/ml threshold. The optimal study design consisted of four groups of children (10 children each), a maximum sampling window of 2 hours in two clinic visits for drawing three samples on day 14 and one on day 28 coinciding with the final examination of the study.

Conclusions

A PK study design was optimised in order to prioritise avoidance of discomfort for enrolled 2–5 year olds by taking only four blood samples from each child and minimising the length of hospital stays.

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Eine verlegte Stirnhöhle mit orbitaler Schwellung

Laryngo-Rhino-Otol 2017; 96: 180-182
DOI: 10.1055/s-0043-103277

© Georg Thieme Verlag KG Stuttgart · New York

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Transplantatgewinnung zur Trommelfellrekonstruktion

Laryngo-Rhino-Otol 2017; 96: 150-150
DOI: 10.1055/s-0043-101420

© Georg Thieme Verlag KG Stuttgart · New York

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Aus der Gutachtenpraxis: Verwechslung von Schilddrüsengewebe und Zenker-Divertikel – ein Behandlungsfehler

Laryngo-Rhino-Otol 2017; 96: 183-184
DOI: 10.1055/s-0043-101413

Hinweis Die Gastautoren des folgenden Beitrages sind Hals-Nasen-Ohren-Arzt (Prof. Ellies) und Viszeralchirurg (Dr. Stapel) und hauptamtlich beim MDK Niederachsen tätig. Sie schildern einen ungewöhnlichen und lehrreichen Fall aus ihrer praktischen Tätigkeit. Zu den Aufgaben des MDK gehört auch die Begutachtung von Behandlungsfehlern im Auftrage von Krankenkassen. Ansprechpartner eines Patienten, der einen Behandlungsfehler vermutet, ist in einem solchen Fall die zuständige Krankenkasse, die sich dann mit dem MDK in Verbindung setzt.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Aktuelle Entwicklung der molekular zielgerichteten Therapie von Kopf-Hals-Karzinomen

Laryngo-Rhino-Otol 2017; 96: 185-198
DOI: 10.1055/s-0043-101412

© Georg Thieme Verlag KG Stuttgart · New York

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Chirurgie der inneren Nase

Laryngo-Rhino-Otol 2017; 96: 201-204
DOI: 10.1055/s-0043-101410

© Georg Thieme Verlag KG Stuttgart · New York

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Comparison of the mechanical properties of different skin sites for auricular and nasal reconstruction

Abstract

Background

Autologous and synthetic nasal and auricular frameworks require skin coverage. The surgeon's decides on the appropriate skin coverage for reconstruction based on colour matching, subcutaneous tissue thickness, expertise and experience. One of the major complications of placing subcutaneous implants is the risk of extrusion (migration through the skin) and infection. However, knowledge of lessening the differential between the soft tissue and the framework can have important implications for extrusion. This study compared the mechanical properties of the skin commonly used as skin sites for the coverage in auricular and nasal reconstruction.

Methods

Using ten fresh human cadavers, the tensile Young's Modulus of the skin from the forehead, forearm, temporoparietal, post-auricular and submandibular neck was assessed. The relaxation rate and absolute relaxation level was also assessed after 90 min of relaxation.

Results

The submandibular skin showed the greatest Young's elastic modulus in tension of all regions (1.28 MPa ±0.06) and forearm showed the lowest (1.03 MPa ±0.06). The forehead demonstrated greater relaxation rates among the different skin regions (7.8 MPa⁻⁰⁷ ± 0.1). The forearm showed the lowest rate of relaxation (4.74 MPa⁻⁰⁷ ± 0.1). The forearm (0.04 MPa ±0.004) and submandibular neck skin (0.04 MPa ±0.005) showed similar absolute levels of relaxation, which were significantly greater than the other skin regions (p < 0.05).

Conclusions

This study provides an understanding into the biomechanical properties of the skin of different sites allowing surgeons to consider this parameter when trying to identify the optimal skin coverage in nasal and auricular reconstruction.

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