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Pharmacokinetics of Desmopressin Administrated as an Oral Lyophilisate Dosage Form in Children With Primary Nocturnal Enuresis and Healthy Adults
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (farmakometri)
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2006 (English)In: Journal of clinical pharmacology, ISSN 0091-2700, E-ISSN 1552-4604, Vol. 46, no 10, 1204-1211 p.Article in journal (Refereed) Published
Abstract [en]

The population pharmacokinetics of desmopressin in children with nocturnal enuresis and in healthy adults were compared using a 1-compartment model with first-order absorption and first-order elimination. In addition, the model consisted of a number of transit compartments before absorption to describe a lag-time. The model gave an adequate description of adult as well as children data and provided a statistically significant better fit to data than a standard lag-time model. The main difference in the pharmacokinetics between children and adults was the absorption delay. The pharmacokinetic difference was minor and presumably of no clinical relevance.

Place, publisher, year, edition, pages
2006. Vol. 46, no 10, 1204-1211 p.
Keyword [en]
Desmopressin, Modeling, Pharmacokinetics, Primary nocturnal enuresis, Transit absorption model
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-97510DOI: 10.1177/0091270006291838ISI: 000240737300012PubMedID: 16988210OAI: oai:DiVA.org:uu-97510DiVA: diva2:172489
Available from: 2008-09-12 Created: 2008-09-12 Last updated: 2017-12-14
In thesis
1. Improved pharmacometric model building techniques
Open this publication in new window or tab >>Improved pharmacometric model building techniques
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pharmacometric modelling is an increasingly used method for analysing the outcome from clinical trials in drug development. The model building process is complex and involves testing, evaluating and diagnosing a range of plausible models aiming to make an adequate inference from the observed data and predictions for future studies and therapy.

The aim of this thesis was to advance the approaches used in pharmacometrics by introducing improved models and methods for application in essential parts of model building procedure: (i) structural model development, (ii) stochastic model development and (iii) model diagnostics.

As a contribution to the structural model development, a novel flexible structural model for drug absorption, a transit compartment model, was introduced and evaluated. This model is capable of describing various drug absorption profiles and yet simple enough to be estimable from data available from a typical trial. As a contribution to the stochastic model development, three novel methods for parameter distribution estimation were developed and evaluated; a default NONMEM nonparametric method, an extended grid method and a semiparametric method with estimated shape parameters. All these methods are useful in circumstances when standard assumptions of parameter distributions in the population do not hold. The new methods provide less biased parameter estimates, better description of variability and better simulation properties of the model. As a contribution to model diagnostics, the most commonly used diagnostics were evaluated for their usefulness. In particular, diagnostics based on individual parameter estimates were systematically investigated and circumstances which are likely to misguide modelers towards making erroneous decisions in model development, relating to choice of structural, covariate and stochastic model components were identified.

In conclusion, novel approaches, insights and models have been provided to the pharmacometrics community.

Implementation of these advances to make model building more efficient and robust has been facilitated by development of diagnostic tools and automated routines.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 98 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 80Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 80
Keyword
Model building, Absorption model, Transit compartment model, Nonparametric method, Extended grid method, Semiparametric, Distribution transformation, Shrinkage, Model diagnostics
Identifiers
urn:nbn:se:uu:diva-9272 (URN)978-91-554-7275-7 (ISBN)
Public defence
2008-10-03, Room B41, BMC, Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-09-12 Created: 2008-09-12Bibliographically approved

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Karlsson, MatsSimonsson, Ulrika

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