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  • 1
    Publication Date: 2014-11-10
    Description: An edge of a perfect graph $G$ is critical if $G-e$ is imperfect. We would like to decide whether $G - e$ is still {\sl almost perfect} or already {\sl very imperfect}. Via relaxations of the stable set polytope of a graph, we define two superclasses of perfect graphs: rank-perfect and weakly rank-perfect graphs. Membership in those two classes indicates how far an imperfect graph is away from being perfect. We study the cases, when a critical edge is removed from the line graph of a bipartite graph or from the complement of such a graph.
    Keywords: ddc:000
    Language: English
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  • 2
    Publication Date: 2020-03-06
    Description: Collection of abstracts of the first SIAM-EMS conference Applied Mathematics in our Changing World'' in Berlin, September 2-6, 2001.
    Keywords: ddc:000
    Language: English
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  • 3
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    Publication Date: 2020-02-11
    Description: {\sc Zimpl} is a little language to translate the mathematical model of a problem into a linear or (mixed-)integer mathematical program expressed in {\tt lp} or {\tt mps} file format which can be read by a LP or MIP solver.
    Keywords: ddc:000
    Language: English
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  • 4
    Publication Date: 2014-02-26
    Description: Im ersten Teil des folgenden Aufsatzes werden allgemeine Überlegungen zur Entwicklung von Bibliotheken hin zu Informationsvermittlungsstellen für sowohl elektronische wie auch gedruckte Medien angestellt. Basierend auf den Ergebnissen der Evaluation digitaler Bibliotheken und Informationsportale in Deutschland wird ein erster Kriterienkatalog für ein Verbund-Informationsportal für den Kooperativen Bibliotheksverbund Berlin-Brandenburg entwickelt. Im Anhang befindet sich der Statusbericht über Informationsportale und digitale Bibliotheken in Deutschland. Dazu wurden sieben digitale Bibliotheken auf Verbundebene und 21 Bibliotheken nach Bundesländern evaluiert.
    Keywords: ddc:000
    Language: German
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  • 5
    Publication Date: 2020-11-13
    Description: Given a set of service requests (events), a set of guided servers (units), and a set of unguided service contractors (conts), the vehicle dispatching problem {\sl vdp} is the task to find an assignment of events to units and conts as well as tours for all units starting at their current positions and ending at their home positions (dispatch) such that the total cost of the dispatch is minimized. The cost of a dispatch is the sum of unit costs, cont costs, and event costs. Unit costs consist of driving costs, service costs and overtime costs; cont costs consist of a fixed cost per service; event costs consist of late costs linear in the late time, which occur whenever the service of the event starts later than its deadline. The program \textsf{ZIBDIP} based on dynamic column generation and set partitioning yields solutions on heavy-load real-world instances (215 events, 95 units) in less than a minute that are no worse than 1\% from optimum on state-of-the-art personal computers.
    Keywords: ddc:000
    Language: English
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  • 6
    Publication Date: 2021-02-01
    Description: Scenario tree models of stochastic programs arise naturally under standard nonanticipativity assumptions. We demonstrate how tree-sparse programs cover the general case, with \emph{arbitrary} information constraints. Detailed examples and intuitive interpretations illuminate the basic thoughts behind the abstract but elementary construction.
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    Language: English
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  • 7
    Publication Date: 2020-03-09
    Description: In this paper we present an algorithm that accelerates 3D texture-based volume rendering of large and sparse data sets. A hierarchical data structure (known as AMR tree) consisting of nested uniform grids is employed in order to efficiently encode regions of interest. The hierarchies resulting from this kind of space partitioning yield a good balance between the amount of volume to render and the number of texture bricks -- a prerequisite for fast rendering. Comparing our approach to an octree based algorithm we show that our algorithm increases rendering performance significantly for sparse data. A further advantage is that less parameter tuning is necessary.
    Keywords: ddc:000
    Language: English
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  • 8
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    Publication Date: 2019-10-24
    Keywords: ddc:000
    Language: German
    Type: annualzib , doc-type:report
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  • 9
    Publication Date: 2021-02-01
    Description: Mathematical optimization techniques are on their way to becoming a standard tool in chemical process engineering. While such approaches are usually based on deterministic models, uncertainties such as external disturbances play a significant role in many real-life applications. The present article gives an introduction to practical issues of process operation and to basic mathematical concepts required for the explicit treatment of uncertainties by stochastic optimization.
    Keywords: ddc:000
    Language: English
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  • 10
    Publication Date: 2014-02-26
    Description: Uncoupling-coupling Monte Carlo (UCMC) combines uncoupling techniques for finite Markov chains with Markov chain Monte Carlo methodology. UCMC aims at avoiding the typical metastable or trapping behavior of Monte Carlo techniques. From the viewpoint of Monte Carlo, a slowly converging long-time Markov chain is replaced by a limited number of rapidly mixing short-time ones. Therefore, the state space of the chain has to be hierarchically decomposed into its metastable conformations. This is done by means of combining the technique of conformation analysis as recently introduced by the authors, and appropriate annealing strategies. We present a detailed examination of the uncoupling-coupling procedure which uncovers its theoretical background, and illustrates the hierarchical algorithmic approach. Furthermore, application of the UCMC algorithm to the $n$-pentane molecule allows us to discuss the effect of its crucial steps in a typical molecular scenario.
    Keywords: ddc:000
    Language: English
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  • 11
    Publication Date: 2021-02-01
    Description: Standard model predictive control for real-time operation of industrial production processes may be inefficient in the presence of substantial uncertainties. To avoid overly conservative disturbance corrections while ensuring safe operation, random influences should be taken into account explicitly. We propose a multistage stochastic programming approach within the model predictive control framework and apply it to a distillation process with a feed tank buffering external sources. A preliminary comparison to a probabilistic constraints approach is given and first computational results for the distillation process are presented.
    Keywords: ddc:000
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  • 12
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    Publication Date: 2021-02-01
    Description: Dynamic stochastic programs are prototypical for optimization problems with an inherent tree structure inducing characteristic sparsity patterns in the KKT systems of interior methods. We propose an integrated modeling and solution approach for such tree-sparse programs. Three closely related natural formulations are theoretically analyzed from a control-theoretic viewpoint and compared to each other. Associated KKT solution algorithms with linear complexity are developed and comparisons to other interior approaches and related problem formulations are discussed.
    Keywords: ddc:000
    Language: English
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  • 13
    Publication Date: 2020-11-13
    Description: We introduce a new problem that was motivated by a (more complicated) problem arising in a robotized assembly enviroment. The bin coloring problem is to pack unit size colored items into bins, such that the maximum number of different colors per bin is minimized. Each bin has size~$B\in\mathbb{N}$. The packing process is subject to the constraint that at any moment in time at most $q\in\mathbb{N}$ bins may be partially filled. Moreover, bins may only be closed if they are filled completely. An online algorithm must pack each item must be packed without knowledge of any future items. We investigate the existence of competitive online algorithms for the online uniform binpacking problem. We show upper bounds for the bin coloring problem. We prove an upper bound of $3q$ - 1 and a lower bound of $2q$ for the competitive ratio of a natural greedy-type algorithm, and show that surprisingly a trivial algorithm which uses only one open bin has a strictly better competitive ratio of $2q$ - 1. Morever, we show that any deterministic algorithm has a competitive ratio $\Omega (q)$ and that randomization does not improve this lower bound even when the adversary is oblivious.
    Keywords: ddc:000
    Language: English
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  • 14
    Publication Date: 2014-02-26
    Description: In circuit switching networks call streams are characterized by their mean and peakedness (two-moment method). The $GI/M/C/0$ system is used to model a single link, where the $GI$-stream is determined by fitting moments appropriately. For the moments of the overflow traffic of a $GI/M/C/0$ system there are efficient numerical algorithms available. However, for the moments of the freed carried traffic, defined as the moments of a virtual link of infinite capacity to which the process of calls accepted by the link (carried arrival process) is virtually directed and where the virtual calls get fresh exponential i.i.d.\ holding times, only complex numerical algorithms are available. This is the reason why the concept of the freed carried traffic is not used rigorously. The main result of this paper is an efficient algorithm for computing the moments of the freed carried traffic, in particular an explicit formula for its peakedness. This result offers a unified handling of both overflow and carried traffics in networks. Furthermore, some refined characteristics for the overflow and freed carried streams are derived.
    Keywords: ddc:000
    Language: English
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  • 15
    Publication Date: 2014-02-26
    Description: In this work we concentrate on developing methods which determine good lower bounds for set partitioning problems (SPP) in an appropriate amount of time. We found out that it makes sense to use the Lagrangian relaxation method for this task. The Lagrangian relaxed problem of SPP has a simple structure, which leads to algorithms and heuristics, whose total complexity per iteration depends linearly on the number of non-zeros of the problem matrix of SPP. In contrast, other methods like simplex methods or interior point methods have a complexity of higher order. Because the problem matrices of our tested instances are sparse, the linear dependence becomes an advantage for the algorithms and heuristics mentioned above. As a reference for the state-of-the-art we have applied the dual simplex method and the barrier function method, implemented in CPLEX. The methods, which we have developed and compared with those of CPLEX, are SBM, CAM, CCBM, and CBM. SBM is a subgradient bundle method derived from the basic subgradient method, which is a global convergent method for determining the maximum of concave functions. CAM is a coordinate ascent method, where the convex coordinate bundle method CCBM and the coordinate bundle method CBM are derivatives from CAM. We observed that the basic subgradient and the coordinate ascent method are improved if bundling techniques can be used. But the motivation for bundling differs for both approaches. In the former case bundling helps to approximate a minimum norm subgradient, which provides a steepest ascent direction, in order to speed up the performance. In the latter case bundling enables proceeding along directions, which are not restricted on the coordinate directions. By this the performance is accelerated. Among all used techniques stabilization is worth mentioning. Stabilization improves the performance especially at the beginning by avoiding too big steps during the proceeding. This leads to a more stabilized progression. Stabilization was successfully applied to SBM, CAM, CCBM, and CBM. As an overall result we conclude the following: \begin{enumerate} \item CPLEX computes the optimal objective values, whereas SBM and CBM has on average a gap of under $1.5\%$. \item In comparison to CPLEX baropt, SBM, CAM, and CBM the algorithm CCBM has a slow convergence because of the convex combination of ascent coordinate directions. An alternative is to relax the convex combination to a simple sum of the corresponding directions. This idea is realized in CBM. \item If we focus on the running time rather than on optimality then CBM is on average the fastest algorithm. \end{enumerate} Note that methods like SBM or CBM are applied on static SPP instances in order to determine a good lower bound. For solving SPP we need dynamical methods. Due to the complex topic of dynamical methods we will not discuss them, but a certain technique is worth mentioning. It is called column generation. We have indicated that this technique needs good Lagrangian multipliers of the corresponding SPP instances in order to generate further columns (in our case duties), which are added to the current SPP instance. Those multipliers are by-products of methods like our six considered methods. Due to the large number of such generation steps the running time depends on the computation time of these methods. Therefore, CBM fits more to this technique than CPLEX baropt or SBM. To sum it up it can be said that applications such as a duty scheduling can be described as set partitioning problems, whose lower bound can be solved by simplex, interior points, subgradient, or coordinate ascent methods. It turns out that the interior points method CPLEX baropt and the heuristic CBM have good performances. Furthermore, good Lagrangian multipliers, which are by-products of these methods, can be used by techniques like column generation. For this particular technique it also turns out that among our tested algorithms CBM is the most efficient one. In general we can state that real-world applications, which have to solve a large number of Lagrangian relaxed SPP instances can improve their performance by using CBM.
    Keywords: ddc:000
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  • 16
    Publication Date: 2014-02-26
    Description: The success of large-scale multi-national projects like the forthcoming analysis of the LHC particle collision data at CERN relies to a great extent on the ability to efficiently utilize computing a management software (Datagrid, Globus, etc.), while the effective integration of computing nodes has been largely neglected up to now. This is the focus of our work. We present a framework for a high-performance cluster that can be used as a reliable computing node in the Grid. We outline the cluster architecture, the management of distributed data and the seamless intergration of the cluster into the Grid environment.
    Keywords: ddc:000
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  • 17
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    Publication Date: 2020-11-13
    Description: Der Aufsatz ist die ausgearbeitete Fassung eines Vortrages, gehalten am 05.04.2001 auf dem 91. Deutschen Bibliothekartag in Bielefeld. Der Kooperative Bibliotheksverbund Berlin-Brandenburg (KOBV) ist im Rahmen eines wissenschaftlichen Projektes in den Jahren 1997 bis 2000 am Konrad-Zuse-Zentrum für Informationstechnik Berlin (ZIB) aufgebaut worden. Nachdem das Projekt erfolgreich abgeschlossen ist, wird der KOBV 2001 institutionalisiert. In dem Vortrag hat die Verfasserin einen Überblick über das bisher Erreichte, den derzeitigen Stand und die Perspektiven des neuen Verbundes gegeben. Der KOBV stellt eine neue Art von Bibliotheksverbund dar. Sein technisches Konzept und sein organisatorischer Aufbau basieren auf der {\sl Internetphilosophie}. Den informationstechnischen Kern bildet eine Suchmaschine, die die heterogenen lokalen Bibliothekssysteme miteinander verbindet. Die KOBV-Organisation ist dezentral. Sie wird getragen von der Kooperation der Bibliotheken in Berlin und Brandenburg. Eine kleine Verbundzentrale koordiniert dieses Geflecht vernetzter lokaler Einheiten, vertritt den KOBV nach außen und arbeitet - in Form von Projekten - an seiner Weiterentwicklung. Der Entwicklungsaspekt und die Nutzerorientierung sind zwei wesentliche Komponenten in der Verbundarbeit. Berlin und Brandenburg haben auf engem Raum zahlreiche Bibliotheken mit großen, reichhaltigen Medienbeständen. Mittel- bis langfristig sollen Bibliotheken aller Sparten und Größen in den KOBV integriert werden, seien es wissenschaftliche Universalbibliotheken, universitäre Bibliothekssysteme, Spezialbibliotheken, Behörden- und Parlamentsbibliotheken oder öffentliche Bibliotheken. Auch regionale Bibliotheksverbünde können als Subverbünde am KOBV teilnehmen. Mit der KOBV-Suchmaschine ist eine offene Plattform geschaffen worden, auf der weitere Entwicklungen aufsetzen können. Der Aufbau einer virtuellen Regionalbibliothek mit Bestell- und Lieferkomponenten ist eines der Ziele. Darüber hinaus ist es die Vision, in der Region ein virtuelles {\sl Wissensportal} aufzubauen, das dem Nutzer unter einer Adresse den umfassenden Zugang und die umfassende Bereitstellung von Informationen aller Art bietet.
    Keywords: ddc:000
    Language: German
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  • 18
    Publication Date: 2019-01-29
    Description: A new approach to the numerical solution of optimal control problems including control and state constraints is presented. Like hybrid methods, the approach aims at combining the advantages of direct and indirect methods. Unlike hybrid methods, however, our method is directly based on interior-point concepts in function space --- realized via an adaptive multilevel scheme applied to the complementarity formulation and numerical continuation along the central path. Existence of the central path and its continuation towards the solution point is analyzed in some theoretical detail. An adaptive stepsize control with respect to the duality gap parameter is worked out in the framework of affine invariant inexact Newton methods. Finally, the performance of a first version of our new type of algorithm is documented by the successful treatment of the well-known intricate windshear problem.
    Keywords: ddc:000
    Language: English
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  • 19
    Publication Date: 2014-02-26
    Description: Das \emph{Committee on Electronic Information and Communication} (CEIC) der \emph{International Mathematical Union} (IMU) hat die Aufgabe, sich über die langfristige Informationsversorgung in der Mathematik Gedanken zu machen und Lösungsvorschläge hierfür zu erarbeiten. Das Kernthema ist natürlich "`Elektronisches Publizieren"'. Dazu gehören auch Copyright-Regelungen. % Sie sind -- % neben einer Andeutung der weiteren CEIC-Pläne -- der Fokus dieses % kurzen Artikels. Er schließt mit einem von der IMU verabschiedeten % Aufruf zu vernünftigem Verhalten bei Copyright-Vereinbarungen. Eine % nachhaltige Befolgung dieses Aufrufs -- verbunden mit weiteren % Aktivitäten -- könnte die (derzeit kaum noch bezahlbare und % dadurch gefährdete) Literaturversorgung nachhaltig zum Positiven % verändern. Mit diesem Artikel beginnt eine kleine Serie von Aufsätzen, in denen ich (in meiner Funktion als eines von elf CEIC-Mitgliedern) die Empfehlungen des CEIC erläutern werde. % Das heutige Thema sind die % CEIC-Vorschläge zum Copyright
    Keywords: ddc:000
    Language: German
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  • 20
    Publication Date: 2019-05-10
    Description: By computed tomography data (CT), the individual geometry of the mandible is quite well reproduced, also the separation between cortical and trabecular bone. Using anatomical knowledge about the architecture and the functional potential of the masticatory muscles, realistic situations were approximated. The solution of the underlying partial differential equations describing linear elastic material behaviour is provided by an adaptive finite element method. Estimations of the discretization error, local grid refinement, and multilevel techniques guarantee the reliability and efficiency of the method.
    Keywords: ddc:000
    Language: English
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  • 21
    Publication Date: 2021-03-19
    Description: Optimization is the task of finding an optimum solution to a given problem. When the decision variables are discrete we speak of a combinatorial optimization problem. Such a problem is online when decisions have to be made before all data of the problem are known. And we speak of a real-time online problem when online decisions have to be computed within very tight time bounds. This paper surveys the are of combinatorial online and real-time optimization, it discusses, in particular, the concepts with which online and real-time algorithms can be analyzed.
    Keywords: ddc:000
    Language: English
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  • 22
    Publication Date: 2014-02-26
    Description: This paper describes a new simulation tool for the prediction of aerosol formation and behavior in gas--liquid contact devices such as absorbers, scrubbers, quench coolers, and condensers as well as multistage gas cleaning processes, respectively. Aerosol formation can impact severely the separation efficiency of gas cleaning processes. Aerosol or fog formation can arise by spontaneous condensation or desublimation in supersaturated gas phases. The rigorous description of the mass and energy transfer between the gas phase, the liquid phase, and the growing aerosol droplets leads to a system of partial differential and algebraic equations. For the solution of these systems we have developed the plant simulation tool AerCoDe. This program bases upon the linearly--implicit Euler discretisation, which in combination with extrapolation permits an adaptive step size and order control. Typical simulation results of a multistage industrial flue gas scrubbing process are presented. It is shown, that experimental data can be confirmed if the number concentration of condensation nuclei as an input parameter is roughly known.
    Keywords: ddc:000
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  • 23
    Publication Date: 2020-11-13
    Description: This paper discusses online optimization of real-world transportation systems. We concentrate on transportation problems arising in production and manufacturing processes, in particular in company internal logistics. We describe basic techniques to design online optimization algorithms for such systems, but our main focus is decision support for the planner: which online algorithm is the most appropriate one in a particular setting? We show by means of several examples that traditional methods for the evaluation of online algorithms often do not suffice to judge the strengths and weaknesses of online algorithms. We present modifications of well-known evaluation techniques and some new methods, and we argue that the selection of an online algorithm to be employed in practice should be based on a sound combination of several theoretical and practical evaluation criteria, including simulation.
    Keywords: ddc:000
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  • 24
    Publication Date: 2014-02-26
    Description: Wireless communication networks employ radio frequencies to establish communication links. The available radio spectrum is very limited. To meet today's radio communication demand, this resource has to be administered and reused carefully in order to control mutual interference. The reuse can be organized via separation in space, time, or frequency, for example. The problem, therefore, arises to distribute frequencies to links in a ``reasonable manner''. This is the basic form of the frequency assignment problem. What ``reasonable'' means, how to quantify this measure of quality, which technical side constraints to consider cannot be answered in general. The exact specification of this task and its mathematical model depend heavily on the particular application considered. In this paper we discuss this issue with respect to the GSM standard for mobile communication.
    Keywords: ddc:000
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  • 25
    Publication Date: 2014-02-26
    Description: This paper is a summary of the Round Table: ``The Impact of Mathematical Research on Industry and Vice Versa'' held at 3ecm in Barcelona on July 11, 2000. The round table started with contributions of the three panelists. Irene Fonseca, the panel chair, opened the discussion by stating six questions addressing the main issues of the round table topic. She presented the panel's answers to these questions, drawing on many examples from her own academic experience. In the following additional presentations, the other two panel members added further points of view based on their personal involvement with industry. The round table ended with a lively discussion with members from the audience. This written summary of the oral presentations follows the structure of the round table indicated above.
    Keywords: ddc:000
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  • 26
    Publication Date: 2020-03-09
    Description: This article is about \emph{adaptive column generation techniques} for the solution of duty scheduling problems in public transit. The current optimization status is exploited in an adaptive approach to guide the subroutines for duty generation, LP resolution, and schedule construction toward relevant parts of a large problem. Computational results for three European scenarios are reported.
    Keywords: ddc:000
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  • 27
    Publication Date: 2014-02-26
    Description: The recent spectral bundle method allows to compute, within reasonable time, approximate dual solutions of large scale semidefinite quadratic 0-1 programming relaxations. We show that it also generates a sequence of primal approximations that converge to a primal optimal solution. Separating with respect to these approximations gives rise to a cutting plane algorithm that converges to the optimal solution under reasonable assumptions on the separation oracle and the feasible set. We have implemented a practical variant of the cutting plane algorithm for improving semidefinite relaxations of constrained quadratic 0-1 programming problems by odd-cycle inequalities. We also consider separating odd-cycle inequalities with respect to a larger support than given by the cost matrix and present a heuristic for selecting this support. Our preliminary computational results for max-cut instances on toroidal grid graphs and balanced bisection instances indicate that warm start is highly efficient and that enlarging the support may sometimes improve the quality of relaxations considerably.
    Keywords: ddc:000
    Language: English
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  • 28
    Publication Date: 2014-02-26
    Description: Der Wissenschaftsrat hat in seiner Juli-Sitzung 2001 \glqq Empfehlungen zur digitalen Informationsversorgung durch Hochschulbibliotheken \grqq verabschiedet. Einige der Vorschläge des Wissenschaftsrates können, falls sie von den angesprochenen Institutionen aufgenommen werden, zu einer nachhaltigen Veränderung der wissenschaftlichen Informationslandschaft führen. In meinem kurzen Kommentar zu diesem Papier möchte ich auf einige dieser Anregungen hinweisen.
    Keywords: ddc:000
    Language: German
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  • 29
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    Publication Date: 2014-02-26
    Description: Von welcher "Informationsumwelt" träumt jemand, der für seine wissenschaftliche (und sonstige) Arbeit digitale Informationstechnologie intensiv einsetzt? In diesem Artikel beschreibe ich meinen "digitalen Traum". Er ist ganz einfach zu formulieren:"Ich will alles und zwar sofort, jederzeit, "überall" und kostenlos zur Verfügung haben." Ich schildere, was davon heute schon (fast) realisiert ist und was noch fehlt. Ich skizziere einige zentrale Schwierigkeiten der vollständigen Realisierung und skizziere mögliche Lösungen.
    Keywords: ddc:000
    Language: German
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  • 30
    Publication Date: 2019-01-24
    Description: Im Rahmen der biomechanischen Simulation knöcherner Organe ist die Frage nach einer befriedigenden Materialbeschreibung nach wie vor ungelöst. Computertomographische Datensätze liefern eine räumliche Verteilung der (Röntgen-)Dichte und ermöglichen damit eine gute Darstellung der individuellen Geometrie. Weiter können die verschiedenen Materialbestandteile des Knochens, Spongiosa und Kortikalis, voneinander getrennt werden. Aber die richtungsabängige Information der Materialanisotropie ist verloren. In dieser Arbeit wird ein Ansatz für eine anisotrope Materialbeschreibung vorgestellt, die es ermöglicht, den Einfluss der individuellen knöchernen Struktur auf das makroskopische Materialverhalten abzuschätzen.
    Keywords: ddc:000
    Language: German
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  • 31
    Publication Date: 2020-03-09
    Description: Many phenomena in nature and engineering happen simultaneously on rather diverse spatial and temporal scales, i.e.\ exhibit a multi-scale character. Therefore various hierarchical data structures and numerical schemes have been devised to represent quantitatively such phenomena. A special numerical multilevel technique, associated with a particular hierarchical data structure, is so-called Adaptive Mesh Refinement (AMR). This scheme achieves locally very high spatial and temporal resolutions. Due to its popularity, many scientists are in need of interactive visualization tools for AMR data. In this article we present a 3D texture-based volume rendering algorithm for AMR data, that directly utilizes the hierarchical structure. Thereby interactive rendering even for large data sets is achieved. In particular the problems of interpolation artifacts, opacity corrections, and texture memory limitations are addressed. The algorithm's value in practice is demonstrated with simulation and image data.
    Keywords: ddc:000
    Language: English
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  • 32
    Publication Date: 2020-03-09
    Description: By combining techniques of preparation, histology, confocal microscopy, data visualization and data processing, we have created and recently published a standard brain model for drosophila and honey bee brains. This report describes the algorithms and implementation of the corresponding software modules. At the same time it serves as a user's guide for scientist who want to reproduce the results for differerent species or mutants.
    Keywords: ddc:000
    Language: English
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  • 33
    Publication Date: 2014-02-26
    Description: Several classes of systems of evolution equations with one or two vector unknowns are considered. We investigate also systems with one vector and one scalar unknown. For these classes all equations having the simplest higher symmetry are listed.
    Keywords: ddc:000
    Language: English
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  • 34
    Publication Date: 2014-02-26
    Description: Two traffic streams $\Phi_1$, $\Phi_2$ are offered a link. The calls of $\Phi_i$ require exponential holding times with parameter $\mu$ and are accepted if less than $C_i$ trunks are occupied. Approximating the $\Phi_i$ by appropriate renewal processes meeting their first two moments, defined as the moments of the numbers of calls in virtual links of infinite capacity to which the traffic streams as freed traffics are virtually directed and where the calls get fresh exponential i.i.d.\ holding times with parameter $\mu$, stable recursive algorithms of complexity $O(\max(C_1,C_2))$ are derived for the first two defined as above moments of the individual overflow and freed carried traffics. The results offer a unified handling of both overflow and carried traffics in circuit switching networks with trunk reservation, providing a basis for new two-moment network dimensioning algorithms.
    Keywords: ddc:000
    Language: English
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  • 35
    Publication Date: 2014-02-26
    Description: We study the performance of QCD simulations with dynamical Wilson fermions by combining the Hybrid Monte Carlo algorithm with parallel tempering on $10^4$ and $12^4$ lattices. In order to compare tempered with standard simulations, covariance matrices between sub-ensembles have to be formulated and evaluated using the general properties of autocorrelations of the parallel tempering algorithm. We find that rendering the hopping parameter $\kappa$ dynamical does not lead to an essential improvement. We point out possible reasons for this observation and discuss more suitable ways of applying parallel tempering to QCD.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 36
    Publication Date: 2020-11-13
    Description: Dem vorliegenden Aufsatz liegt ein Vortrag zugrunde, den die Verfasserin auf der Ersten Gemeinsamen Fachtagung der DBV-Landesverbände Berlin und Brandenburg "Wir machen den Weg frei : Fusionen - Kooperationen in Berlin und Brandenburg" am 17. Oktober 2001 gehalten hat, in der Vortragsreihe "Möglichkeiten und Grenzen von Ausleih- und bibliographischen Verbünden - VÖB Berlin, VÖB Brandenburg, KOBV". Der Kooperative Bibliotheksverbund Berlin-Brandenburg (KOBV) ist angetreten, um auf der Basis neuer Technologien zeitgemäße, nutzerorientierte Dienstleistungen für den Informationsbereich zu entwickeln und die Informationsinfrastruktur in der Region Berlin-Brandenburg neu zu organisieren. Dabei setzt der KOBV insbesondere auf das Internet. Die Verfasserin beschreibt die einzelnen Stufen, in denen die Dienste des KOBV aufgebaut wurden und kontinuierlich weiter ausgebaut werden. Dabei zeigt sie Vorteile auf, die Nutzern und Bibliotheken durch den Verbund entstehen, und lotet gleichzeitig die Grenzen aus, die dem Verbund gesetzt sind.
    Keywords: ddc:000
    Language: German
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  • 37
    Publication Date: 2014-02-26
    Description: We report numerical results for SBmethod --- a publically available implementation of the spectral bundle method --- applied to the 7$^{th}$ DIMACS challenge test sets that are semidefinite relaxations of combinatorial optimization problems. The performance of the code is heavily influenced by parameters that control bundle update and eigenvalue computation. Unfortunately, no mathematically sound guidelines for setting them are known. Based on our experience with SBmethod, we propose heuristics for dynamically updating the parameters as well as a heuristc for improving the starting point. These are now the default settings of SBmethod Version 1.1. We compare their performance on the DIMACS instances to our previous best choices for Version 1.0. SBmethod Version 1.1 is also part of the independent DIMACS benchmark by H.~Mittelmann. Based on these results we try to analyze strengths and weaknesses of our approach in comparison to other codes for large scale semidefinite programming.
    Keywords: ddc:000
    Language: English
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  • 38
    Publication Date: 2014-11-10
    Description: Many {\cal NP}-hard graph problems can be solved in polynomial time for graphs with bounded treewidth. Equivalent results are known for pathwidth and branchwidth. In recent years, several studies have shown that this result is not only of theoretical interest but can successfully be applied to find (almost) optimal solutions or lower bounds for diverse optimization problems. To apply a tree decomposition approach, the treewidth of the graph has to be determined, independently of the application at hand. Although for fixed $k$, linear time algorithms exist to solve the decision problem ``treewidth $\leq k$'', their practical use is very limited. The computational tractability of treewidth has been rarely studied so far. In this paper, we compare four heuristics and two lower bounds for instances from applications such as the frequency assignment problem and the vertex coloring problem. Three of the heuristics are based on well-known algorithms to recognize triangulated graphs. The fourth heuristic recursively improves a tree decomposition by the computation of minimal separating vertex sets in subgraphs. Lower bounds can be computed from maximal cliques and the minimum degree of induced subgraphs. A computational analysis shows that the treewidth of several graphs can be identified by these methods. For other graphs, however, more sophisticated techniques are necessary.
    Keywords: ddc:000
    Language: English
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  • 39
    Publication Date: 2014-02-26
    Description: The currently most efficient algorithm for inference with a probabilistic network builds upon a triangulation of a network's graph. In this paper, we show that pre-processing can help in finding good triangulations for probabilistic networks, that is, triangulations with a minimal maximum clique size. We provide a set of rules for stepwise reducing a graph, without losing optimality. This reduction allows us to solve the triangulation problem on a smaller graph. From the smaller graph's triangulation, a triangulation of the original graph is obtained by reversing the reduction steps. Our experimental results show that the graphs of some well-known real-life probabilistic networks can be triangulated optimally just by preprocessing; for other networks, huge reductions in their graph's size are obtained.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 40
    Publication Date: 2014-11-11
    Description: {\begin{rawhtml} 〈a href="http://dx.doi.org/10.1007/s10479-007-0178-0"〉 Revised Version unter http://dx.doi.org/10.1007/s10479-007-0178-0〈/a〉 \end{rawhtml}} Wireless communication is used in many different situations such as mobile telephony, radio and TV broadcasting, satellite communication, and military operations. In each of these situations a frequency assignment problem arises with application specific characteristics. Researchers have developed different modelling ideas for each of the features of the problem, such as the handling of interference among radio signals, the availability of frequencies, and the optimization criterion. This survey gives an overview of the models and methods that the literature provides on the topic. We present a broad description of the practical settings in which frequency assignment is applied. We also present a classification of the different models and formulations described in the literature, such that the common features of the models are emphasized. The solution methods are divided in two parts. Optimization and lower bounding techniques on the one hand, and heuristic search techniques on the other hand. The literature is classified according to the used methods. Again, we emphasize the common features, used in the different papers. The quality of the solution methods is compared, whenever possible, on publicly available benchmark instances.
    Keywords: ddc:000
    Language: English
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  • 41
    facet.materialart.
    Unknown
    Publication Date: 2014-02-26
    Description: Telota ist ein Kunstwort, das für alle Aktivitäten der Berlin-Brandenburgischen Akademie der Wissenschaften steht, die der Förderung von Forschung, Kommunikation und Präsentation durch elektronische Medien dienen. In diesem Artikel werden die Entstehung des Telota-Projektes geschildert und die Ziele diskutiert, die mit diesem Projekt erreicht werden sollen. Es geht darum, moderne Informationstechnik bewusst, geplant und nachhaltig für alle Belange der {\rm BBAW} einzusetzen. Informationstechnische Werkzeuge sollen für die wissenschaftliche Arbeit effizient genutzt werden; die Information nach innen und nach außen soll deutlich verbessert werden; eine bessere Kommunikationsinfrastuktur soll die Zusammenarbeit fördern.
    Keywords: ddc:000
    Language: German
    Type: reportzib , doc-type:preprint
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  • 42
    Publication Date: 2022-07-07
    Description: The pole condition is a general concept for the theoretical analysis and the numerical solution of a variety of wave propagation problems. It says that the Laplace transform of the physical solution in radial direction has no poles in the lower complex half-plane. In the present paper we show that for the Helmholtz equation with a radially symmetric potential the pole condition is equivalent to Sommerfeld's radiation condition. Moreover, a new representation formula based on the pole condition is derived and used to prove existence, uniqueness and asymptotic properties of solutions. This lays the foundations of a promising new algorithm to solve time-harmonic scattering problems numerically and provides a new approach for analyzing existing algorithms such as the Perfectly Matched Layer (PML) method and the Bayliss-Gunzburger-Turkel (BGT) algorithm.
    Keywords: ddc:000
    Language: English
    Type: reportzib , doc-type:preprint
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  • 43
    Publication Date: 2022-07-07
    Description: In this paper we study the PML method for Helmholtz-type scattering problems with radially symmetric potential. The PML method consists in surrounding the computational domain by a \textbf{P}erfectly \textbf{M}atched sponge \textbf{L}ayer. We prove that the approximate solution obtained by the PML method converges exponentially fast to the true solution in the computational domain as the thickness of the sponge layer tends to infinity. This is a generalization of results by Lassas and Somersalo based on boundary integral eqaution techniques. Here we use techniques based on the pole condition instead. This makes it possible to treat problems without an explicitly known fundamental solution.
    Keywords: ddc:000
    Language: English
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  • 44
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 631-634 
    ISSN: 1432-1041
    Keywords: salbutamol ; albuterol ; pharmacokinetics ; bioavailability ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Salbutamol was administered to sixteen healthy male volunteers intravenously and by mouth in liquid, tablet, and capsule form using a Latin-Squares design. Pharmacokinetic parameters from intravenous data were similar to previously reported values obtained with oral administration, with a mean terminal half-life of 3.8 h and a mean clearance of 439 ml·min−1·1.73 m−2. Peak plasma concentrations of 10–20 ng·ml−1 were obtained 1–3 h following oral administration. The absolute bioavailability of each of the oral preparations was 44%. While statistically significant differences in lag time and time to peak concentration were noted among the various oral preparations, the drug is rapidly absorbed in all three dosage forms and the observed differences are unlikely to be of clinical significance.
    Type of Medium: Electronic Resource
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  • 45
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 411-418 
    ISSN: 1432-1041
    Keywords: 5-fluorouracil ; colorectal carcinoma ; pharmacokinetics ; product-inhibition ; blood clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The nonlinear disposition kinetics of 5-fluorouracil (5-FU) were investigated in 6 patients with colorectal carcinoma. Each patient randomly received two single, intravenous doses of 5-FU (7.5 and 15 mg/kg) on separate days. Venous blood and urine samples were collected just prior to and for 5 h after drug administration. In addition to the kinetic studies, the in vitro whole blood/plasma concentration ratio and stability of 5-FU at 37°C were determined in whole blood from normal volunteers and from 5 patients with colorectal carcinoma. A disproportionate increase in area under the curve and corresponding decrease in total body clearance with increasing dose was observed suggesting dose-dependent behavior of 5-FU. Doubling the dose was accompanied by a 36% decrease in nonrenal clearance but no apparent change in renal clearance. Therefore, the mechanism for dose-dependent elimination appears to be primarily associated with nonrenal processes. The mean 5-FU half-life following the high dose was nearly twice as long as that observed for the low dose (12.3 versus 6.2 min). The log-linear decline in plasma concentrations and increase in half-life with dose suggest the potential role of product-inhibition as an explanation for the observed nonlinearity in 5-FU elimination. The present study demonstrates that 5-FU degrades when incubated in whole blood. This most likely reflects metabolism in red blood cells or other blood-formed elements since 5-FU was stable in plasma. Although degradation in whole blood occurs, the estimated whole blood clearance does not contribute significantly to the observed total body clearance value. These findings suggest the possibility of pulmonary clearance of 5-FU.
    Type of Medium: Electronic Resource
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  • 46
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 431-432 
    ISSN: 1432-1041
    Keywords: theophylline ; fluoroquinolones ; drug interaction ; pharmacokinetics ; ofloxacin ; norfloxacin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pretreatment for 3 days with oral ofloxacin or norfloxacin had no significant effect on the disposition of a single i.v. dose the theophylline in healthy volunteers.
    Type of Medium: Electronic Resource
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  • 47
    ISSN: 1432-1041
    Keywords: growth hormone releasing factor ; radio-immunoassay ; pharmacokinetics ; variance model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Three ranges of doses of growth hormone releasing factor (2.5–80 µg, 80–320 µg and 75–600 µg) were intravenously administered to healthy young volunteers in three double blind studies. Serum circulating GRF levels were determined by radioimmunoassay. Experimental concentration curves were fitted, using the extended least squares method, to a biexponential model for the structural model and power function for the variance model. The power variance model, compared to the constant variance model greatly reduced the coefficient of variation of the biexponential parameters. The power of the variance model was estimated to be 1.95. The distribution half-life was 6.6 min and the elimination half-life was 39.0 min (harmonic means). Total clearance was 0.12±0.01 µg/l/min. No difference between these parameters was found for the various doses. GRF kinetics was linear established in the range 10 to 600 µg which means that elimination was not altered by the increased doses.
    Type of Medium: Electronic Resource
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  • 48
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 563-568 
    ISSN: 1432-1041
    Keywords: nitrendipine ; pharmacokinetics ; hepatitis ; liver cirrhosis ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwords nitrendipine 20 mg once daily were administered orally for seven days. With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0–24), was 94.5 ng ml−1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0–24) h was significantly greater at 309.4 ng ml−1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance. Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.
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  • 49
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 597-605 
    ISSN: 1432-1041
    Keywords: iloprost ; prostacyclin analogue ; pharmacokinetics ; pharmacodynamics ; radiolabeled study ; volunteers ; side-effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels and excretion of tritium-labeled iloprost in healthy elderly male and female volunteers have been measured after i.v. infusion of 2 ng·kg−1·min−1 for 4 h and oral administration of 0.1 and 0.48 μg/kg. During infusion, a steady-state of labeled compounds in the plasma was not achieved. Total radioactivity declined from a mean of 408 pg equiv/ml in three phases, with half-lives of 24 min, 1.7 h and 5.0 h, respectively. A steady-state of unchanged iloprost was reached rapidly with a peak of 81 pg/ml. Plasma levels declined biphasically with half-lives of 6 min and 31 min. Total clearance was 24 ml· min−1·kg−1. Maximum concentrations of labeled substances after oral administration were 307 and 1,051 pg equiv/ml after 29 and 39 min respectively. The peak of unchanged iloprost (116 pg/ml) was observed 7.5 min after an oral dose of 0.48 μg/kg. Bioavailability was 16%. Iloprost was totally metabolized and the metabolities were mainly excreted in urine. The main biotransformation products in plasma and urine were tentatively identified by cochromatography as dinor-and tetranoriloprost and their glucuronides. ADP-induced platelet aggregation was reduce by 60% during the i.v. infusion and 15 min after oral administration of 0.48 μg/kg. Heart rate and blood pressure were virtually unaffected. Common side-effects were facial flush, headache and nausea.
    Type of Medium: Electronic Resource
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  • 50
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 32 (1987), S. 625-629 
    ISSN: 1432-1041
    Keywords: disopyramide ; bioavailability ; saturable binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of disopyramide were determined in 10 healthy volunteers after a 300 mg oral dose and again after a 2mg/kg i.v. dose. The unbound clearance was 599 ml/min and the unbound renal clearance 310 ml/min. The terminal elimination rate constant of unbound drug was 0.180 h−1 after the i.v. dose and 0.203 h−1 after the oral dose. The absorption rate constant was 0.53−1 and the maximum peak concentration occurred after 3.2 h. The bioavailability was 0.809 using the area under the unbound plasma concentration time curve. Although a saturable plasma protein binding was found in all subjects the bioavailability using the total concentration, in contrast to theoretical expectations, showed the same value (0.813) as the unbound concentrations.
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  • 51
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 197-201 
    ISSN: 1432-1041
    Keywords: ceftazidime ; renal impairment ; plasmapheresis ; pharmacokinetics ; cephalosporins ; autoimmune disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of plasmapheresis (PA) on the elimination kinetics of ceftazidime (Cef) has been investigated. A single dose of Cef was administered intravenously to 11 patients with autoimmune diseases and varying degrees of renal impairment (Group I CLCR〈50 ml/min, Group II CLCR〉50 ml/min). In Groups I and II the mean total clearance of Cef (CL) was 30 and 116 ml/min−1, respectively. The elimination half-life (t1\2β) and the volume of distribution (V) were significantly higher in Group I than in Group II (11.9 vs 2.0 h, 27.1 vs 18.5 l). PA had no influence on the plasma level-time profile of Cef. The amount of Cef recovered from separated plasma accounted for only 2 to 9% of the administered dose, being particularly low in patients with normal renal function (4.6%). Thus, since elimination of Cef via PA is negligible, dosage calculations should be based solely on renal function.
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  • 52
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 227-230 
    ISSN: 1432-1041
    Keywords: enoxacin ; theophylline ; drug interaction ; healthy volunteers ; adverse effects ; pharmacokinetics ; renal tubular excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The mechanism of the theophylline-enoxacin interaction has been studied in six healthy subjects. Theophylline 250 mg was administered p.o., twice daily for 11 days in a sustained release dosage form. On the 4th day of treatment, blood samples were taken every 2 h and urine was collected over 1 dose interval. From Days 5 to 11 coated tablets of enoxacin 400 mg b.i.d. were coadministered. On Day 11 blood and urine were collected as on Day 4. The mean plasma theophylline concentration rose from 4.4 to 15.1 mg/l, corresponding to a 73.6% reduction in total clearance. The urinary excretion of unchanged theophylline increased from 12.7 to 35.3%, whereas the production of metabolites was reduced (1-demethylation 81.4%; 3-demethylation 83.1%, 8-hydroxylation 74.6%). The results indicate that the theophylline-enoxacin interaction may be due to inhibition of the cytochrome P-450 isozymes responsible for theophylline metabolism. Unexpectedly, the renal clearance of theophylline metabolites was found to be drastically reduced when enoxacin was coadministered. This led to unchanged or even to elevated plasma levels of the metabolites. The mechanism of this interaction is still to be elucidated, but it may be due to competition for renal tubular secretion.
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  • 53
    ISSN: 1432-1041
    Keywords: iron deficiency anaemia ; sulphadimidine ; absorption ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of iron deficiency anaemia and its treatment on the absorption of sulphadimidine has been investigated in adult patients. The absorption judged by total % of the dose excreted in urine and Cmax, tmax, AUC and Kabs in plasma, was not significantly different before and after iron therapy or correction of anaemia. However, sulphadimidine absorption by the anaemic patients was significantly greater than in normals.
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  • 54
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 315-318 
    ISSN: 1432-1041
    Keywords: propranolol ; pharmacodynamics ; pharmacokinetics ; beta-blockade ; sustained-release propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The duration and extent of cardiac beta-blockade and their relationship to propranolol pharmacokinetics were assessed in nine healthy volunteers. Each subject received 160 mg of regular propranolol (R), 160 mg of sustained-release propranolol (SR) and no drug (control), both as single doses and once daily for 7 days. After single doses and at steady-state, both products caused a decrease in exercise heart rate for at least 24 h, compared to control. The time course of effect was similar to the time course of serum propranolol concentration. The oral clearance of propranolol decreased from single doses to steady-state for both R and SR; however, the difference achieved statistical significance only for R. These changes were reflected in mean accumulation ratios (AUC steady-state 0–24 h/AUC single dose 0-infinity) of 1.49 and 1.68 for R and SR, respectively. The pharmacokinetic data are consistent with a decrease in intrinsic hepatic clearance of propranolol, leading to an increase in bioavailability at steady-state. Despite a two-fold difference in the bioavailability of R and SR, there was no difference in the area under the effect-time curve at steady-state.
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  • 55
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 355-361 
    ISSN: 1432-1041
    Keywords: metoprolol ; smoking ; gender ; pharmacokinetics ; HPLC ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous infusion over 20 min. The only significant difference between smokers (S) and nonsmokers (NS) was that S had a larger steady-state volume of distribution (3.3 vs 2.5 l/kg). There were no differences in half-life, systemic clearance or bioavailability (f). No differences were observed between males (M) and females (FM) for any of the kinetic parameters examined. Systemic bioavailability varied markedly between subjects (range: 15 to 92%). In fifteen of the eighteen subjects, f was higher after the 200-mg dose compared to the 100-mg dose. These results suggest that metoprolol may be subject to saturable presystemic elimination and extend the previous observations of Johnsson et al. [1] who showed that f increased from 31% to 46% when doses were increased from 20 to 100 mg. However, the difference in f as the dose is increased is unlikely to be clinically significant since the mean difference is smaller than the variation in f among subjects.
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  • 56
    ISSN: 1432-1041
    Keywords: amodiaquine ; Plasmodium falciparum malaria ; monodesethylamodiaquine ; HPLC ; pharmacokinetics ; prophylaxis ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of monodesethylamodiaquine was studied in four healthy subjects after a single oral dose of 10 mg/kg amodiaquine base. Amodiaquine was not found in any sample, but the major metabolite monodesethylamodiaquine was detected and was assumed to be the sole derivative that contributed significantly to antimalarial activity in the blood. The best fit for the decay of the metabolite was obtained with a three-compartment model. The half-lives of the first two phases were 3.2 to 11.4 h for t1/2α1 and 22.7 to 50.3 h for t1/2α2 in plasma. The half-life of the terminal phase ( t1/2β) was between 9 and 18.2 days. The concentration in whole blood was 4- to 6-times higher than in plasma. Three schedules (alternate days, weekly, daily) of the conventional prophylactic dose of 10 mg/kg per week were compared in six other healthy subjects. There were significant differences in the plasma monodesethylamodiaquine levels between the three schedules.
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  • 57
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    European journal of clinical pharmacology 33 (1987), S. 423-426 
    ISSN: 1432-1041
    Keywords: Ketanserin ; pharmacokinetics ; hypertension ; ketanserinol ; predicted plasma concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of ketanserin in 6 hypertensive patients after a single oral 40 mg dose and at steady-state after 4 weeks treatment with 20 mg and then 40 mg 12-hourly. Pharmacokinetic variables after a single dose were similar to those reported in healthy volunteers, with median values for Cmax 112 ng·ml−1, tmax 1 h, and t1/2 19 h. The corresponding values for the metabolite ketanserinol were Cmax 155 ng·ml−1, tmax 2 h, and t1/2 25 h. The median AUC was 3.3 times greater for ketanserinol than for the parent drug. These results were used to predict the mean steady-state plasma concentrations of ketanserin and ketanserinol. Predicted values were on average similar to those observed after four weeks treatment with 40 mg 12-hourly, although there were marked differences between the observed and predicted values in some patients. There was no evidence of time- or dose-dependent kinetics for ketanserin, but the study had insufficient power to exclude the occurrence of these phenomena entirely.
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  • 58
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    European journal of clinical pharmacology 33 (1987), S. 531-534 
    ISSN: 1432-1041
    Keywords: ketoconazole ; pharmacokinetics ; antimycotic drug
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of the anti-mycotic ketoconazole in seven patients who took it for 1–6 months at a dose of 200 mg daily. The mean elimination half-life of the drug was 3.3 h, and although the ketoconazole was given only once daily, a satisfactory clinical response was obtained in all seven individuals. Only a small fraction of the absorbed drug (mean 0.22%) was excreted unchanged in the urine, suggesting almost complete metabolism. Our results support the concept that anti-mycotic activity in the tissues continues after the plasma drug concentration has fallen below a critical level. Our results also support the concept of a change in pharmacokinetics with chronic dosing.
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  • 59
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    European journal of clinical pharmacology 33 (1987), S. 67-72 
    ISSN: 1432-1041
    Keywords: cisplatin ; pharmacokinetics ; modelling ; drug dispositions ; cancer patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have fitted a first-order multicompartment pharmacokinetic model to plasma platinum concentrations measured in nine ovarian cancer patients who received intravenous infusions of cisplatin for 6 h. The time-course of ultrafilterable plasma platinum was similar in all patients studied, and was fitted by a single compartment within the limits of experimental detection. However, the time-course of protein-bound platinum showed marked differences between patients, the differences being explained by distribution to two peripheral compartments. The wide inter-patient variation observed in protein-bound plasma platinum concentrations supports the view that pharmacokinetic modelling should be carried out separately for each patient, since averaging plasma concentrations would have obscured some individual pharmacokinetic characteristics.
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  • 60
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    European journal of clinical pharmacology 33 (1987), S. 59-65 
    ISSN: 1432-1041
    Keywords: indoramin ; 6-hydroxyindoramin ; debrisoquine ; hydroxylators ; genetic polymorphism ; blood pressure ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five poor metabolisers (PM) and seven extensive metabolisers (EM), of debrisoquine, all healthy volunteers, received 50 mg indoramin orally following an overnight fast. Plasma concentrations of indoramin and 6-hydroxyindoramin were determined by HPLC with fluorimetric detection. In PM subjects, mean values of Cmax (158 ng/ml) and AUC(0–24) (2556 ng·h·m−1) for indoramin were substantially elevated and t1/2β (18.5 h) prolonged by comparison with values in the EM subjects (21.6 ng/ml, 151 ng·h·ml−1 and 5.2 h respectively). For 6-hydroxyindoramin, on the other hand, Cmax (12.4 ng/ml) and AUC(0–8) (47.5 ng·h·ml−1) in PM subjects were significantly lower than in the EM subjects (28.2 ng/ml and 94.7 ng·h·ml−1). There was a tendency to a higher incidence of side-effects in the PM group. Although the difference did not achieve statistical significance (0.1〉p〉0.05), all the PM subjects experienced sedation compared to only two in the EM group. Differences in blood pressure and pulse rate between the two groups were small. It is concluded that the oxidative metabolism of indoramin is subject to genetic polymorphism, which is probably under the control of the same gene locus as that influencing debrisoquine oxidation. The clinical consequences are discussed.
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  • 61
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    European journal of clinical pharmacology 33 (1987), S. 179-183 
    ISSN: 1432-1041
    Keywords: aminoglycosides ; haemodialysis ; gentamicin ; tobramycin ; pharmacokinetics ; renal failure ; kanamycin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The study was undertaken to look for a correlation between the measured elimination rate constants (k) of aminoglycosides and creatinine during haemodialysis. The pharmacokinetics of aminoglycosides were studied during 44 courses of haemodialysis in 21 patients. The measured k of gentamicin and tobramycin from the start until 30 min after the end of haemodialysis (mean 0.18 h−1; t1/2=3 h 51 min) was significantly correlated with the measured k of creatinine (mean 0.13 h−1; t1/2=5 h, 20 min), and also with the gentamicin and tobramycin k during haemodialysis (mean 0.20 h−1, t1/2=3 h, 28 min), as predicted by a computer program. Thus, serum concentrations of aminoglycosides 30 min after haemodialysis can be estimated by simple regression equations. However, because the measured and predicted values may diverge considerably in the individual patient, monitoring of aminoglycoside concentrations in serum after haemodialysis remains necessary.
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  • 62
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    European journal of clinical pharmacology 33 (1987), S. 287-292 
    ISSN: 1432-1041
    Keywords: praziquantel ; cysticercosis ; pharmacokinetics ; cerebrospinal fluid ; parasite drug level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two patients with cysticercosis received praziquantel (PZQ) 75 mg/kg/day orally together with 30 mg prednisone daily for 3 weeks. The first patient presented with grand-mal seizures, a pyramidal tract syndrome and subcutaneous cysticerci, and the other had internal hydrocephalus necessitating drainage. Serial plasma samples were taken after the first dose of PZQ. Lumbar CSF was obtained from the first patient and ventricular CSF from the second. Subcutaneous cysticerci were removed from the first patient. PZQ in the specimens was assayed by GLC. For distribution between plasma and CSF a rate constant of 4.9 h−1 for free PZQ, corresponding to a t1/2 of 8 min or less for the non-protein bound fraction was calculated for Patient 1. In the second patient the distribution was so rapid that the rate constant could not be calculated. The difference in distribution rate might have been due to use of different sampling times or to a time lag in the entry of PZQ between the ventricles and the lumbar sac. The rate constant for distribution of the drug between plasma and parasites was 1.4 h−1, corresponding to a t1/2 of 30 min or less. Thus PZQ penetrates rapidly into the CSF. It enters the parasite more slowly, although still more rapidly than the plasma half-life of PZQ (1–1 1/2 h).
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  • 63
    ISSN: 1432-1041
    Keywords: metoprolol ; neonates ; amniotic fluid ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven women were treated with metoprolol 50–100 mg twice daily for hypertension in pregnancy. The disposition of metoprolol and one of its metabolites alfa-OH-metoprolol was studied in venous plasma and amniotic fluid during labour, in mixed cord plasma and in capillary blood of the newborn. Peak concentrations of metoprolol and alfa-OH-metoprolol were reached 60 to 120 min after dosing in maternal plasma while the amniotic fluid levels of these compounds continued to increase from 60 to 180 min to the end of the study and were substantially higher than in the plasma after 4 to 5 h. It is postulated that a major fraction of metoprolol and alfa-OH-metoprolol reaches the amniotic fluid via the fetal urine and that the elimination from the amniotic fluid mainly proceeds via diffusion across fetal membranes and transfer across the fetal capillary bed. No measurable concentrations of metoprolol were found in two of the newborns 2 h after delivery. In the remaining four neonates the 2-h concentrations exceeded the corresponding cord plasma levels. In all neonates the alfa-OH-metoprolol levels in the capillary blood were higher 2 h after birth than in cord blood. In two newborns the metabolite levels continued to increase for 5 h and in one the highest blood concentrations of this metabolite was found 20 h after birth. Redistribution of metoprolol from tissue stores followed by metabolism might be the cause of these temporary elevations of the blood levels of metoprolol and alfa-OH-metoprolol.
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  • 64
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    European journal of clinical pharmacology 33 (1987), S. 431-434 
    ISSN: 1432-1041
    Keywords: phenylethylmalonamide ; pharmacokinetics ; elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of phenylethylmalonamide (PEMA) were studied in 6 elderly men after oral administration of a single 400 mg dose. Peak PEMA serum levels were obtained within 4 h of intake, half-life values ranged from 30.7–57.9 h in these elderly men. The elimination half-life was twice as long when compared to a study previously performed in young volunteers.
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  • 65
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    European journal of clinical pharmacology 33 (1987), S. 493-498 
    ISSN: 1432-1041
    Keywords: amiloride ; pharmacokinetics ; renal failure ; liver disease ; urinary excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the antikaliuretic amiloride has been studied in healthy controls and in patients with chronic renal failure or hepatitis. It was 40% bound to protein. In healthy volunteers 49% of an oral dose was recovered unchanged in the urine. The renal clearance of amiloride was about 3 times the creatinine clearance, which means that it was predominantly excreted via tubular secretion. Renal impairment reduced the clearance of amiloride, causing a prolongation of the t1/2 and drug accumulation in plasma. In hepatitis the t1/2 of amiloride was prolonged and the AUC increased. Urinary recovery (Ae) of amiloride was greater in hepatitis patients than in controls.
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  • 66
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    European journal of clinical pharmacology 33 (1987), S. 499-504 
    ISSN: 1432-1041
    Keywords: morphine ; epidural administration ; pharmacokinetics ; CSF/plasma concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In order to determine the rate and degree of redistribution of morphine within the cerebrospinal fluid (CSF), and whether it was affected by the site of and volume of the injection, morphine was given to 23 elderly patients undergoing thoracotomy — in 10 ml saline in the lumbar epidural interspace (n=5), in 10 ml saline in the thoracic epidural interspace (n=5), in 2 ml saline in the thoracic interspace (n=8) and in 10 ml saline in the lumbar epidural interspace (n=5). The plasma concentration of morphine in all patients was comparable and was much lower than in the CSF. The CSF morphine concentration, measured as the area under the CSF concentration curve (AUC), the maximal CSF concentration (Cmax) and the time to reach maximal CSF concentration (tmax), varied between the four groups. The variation was related to the site of the injection; the AUC and Cmax were lower and tmax appeared later after thoracic than lumbar injection. Lumbar CSF morphine concentrations were further reduced by thoracic epidural injection of morphine in a small as compared to a large volume. The permeability of the dura to morphine was not influenced by the volume used. The results show that morphine is not homogenously distributed within the CSF. The availability of morphine to CSF from the epidural space is not altered by the injection volume, but the drug remains more localized in CSF after epidural injection of morphine in a small volume. The findings imply that epidural injection of morphine in a small volume at a site of nociceptive input should evoke spinal analgesia with least risk of supraspinally mediated side effects.
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  • 67
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    European journal of clinical pharmacology 32 (1987), S. 273-277 
    ISSN: 1432-1041
    Keywords: pentobarbital ; hexobarbital ; dipyrone ; intensive care ; D-glucaric acid ; pharmacokinetics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of pentobarbital treatment in a mean dose of 30 mg/kg/day on the clearance of hexobarbital (Evipan) and dipyrone (Novalgin) has been evaluated in critical care patients receiving a large number of drugs as comedication. Eleven patients treated with pentobarbital showed a hexobarbital half-life of 2.79 h and a total plasma clearance of 9.80 ml·min−1·kg−1 as compared to 10 patients without pentobarbital administration in whom there was a significantly longer half life (6.92 h) and lower clearance (2.97 ml·min−1·kg−1). The kinetics of hexobarbital were correlated with the urinary excretion of D-glucaric acid, a non-invasive parameter of drug metabolising activity. In 10 patients on pentobarbital, the total plasma clearance of N-4-methylaminoantipyrine, the active form of dipyrone, did not differ from that in 8 patients not receiving pentobarbital. As drug kinetics show great variability in these patients, it is difficult to discriminate enzyme induction from other mechanisms, for example competitive inhibition or changes in volume of distribution. In the presence of pentobarbital, however, induction of drug metabolising enzymes should be considered as a possible reason for the higher clearance of hexobarbital.
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  • 68
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    European journal of clinical pharmacology 32 (1987), S. 367-372 
    ISSN: 1432-1041
    Keywords: endralazine ; severe hypertension ; food intake ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A sensitive HPLC assay has been used to determine the effect of food on plasma endralazine levels in 8 patients with essential hypertension. Subjects were investigated whilst on maintenance therapy with endralazine combined with a fixed antihypertensive baseline treatment for at least 4 weeks, samples being collected after the usual oral morning dose of endralazine (5 mg and 10 mg), on two occasions at least 7 days apart. Endralazine was administered with the concomitant therapy in randomised order once 90 min before and once immediately after a standard breakfast. Acetylator status did not affect its pharmacokinetics in the postprandial study after a 5 mg dose, the peak endralazine concentration averaged 57.5% lower and the AUC had fallen significantly by 49.9%, whereas after 10 mg the postprandial peak level and the AUC were 82.9% and 64.7%, lower. In the 5 mg study the mean arterial blood pressure was decreased by 30 mm Hg in the fasting subjects and by 21 mm Hg in the post-prandial group. For the 10 mg dose the corresponding values were 35 and 24 mm Hg. The blood pressure lowering effect was only weakly correlated with the food — related reduction in the plasma endralazine levels. The results suggest that endralazine has a similar kinetic interaction with food as that found for hydralazine.
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  • 69
    ISSN: 1432-1041
    Keywords: triazolam ; troleandomycin ; benzodiazepines ; antibiotics ; drug interaction ; pharmacokinetics ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven healthy volunteers received a single oral dose of triazolam 0.25 mg after 7 days on troleandomycin 2 g/day p.o. or placebo in a double-blind cross-over study. Plasma triazolam and psychometric and memory tests (including Critical Flicker Fusion threshold, Choice Reaction Time, Digit Symbol Substitution and Self-Rating Scales) were assessed at regular intervals after the final treatment. Troleandomycin was found to prolong the psychomotor impairment and amnesia produced by triazolam. There was a significant enhancement of the AUC, the peak concentration and the delay to tmax of triazolam after 7 days treatment with troleandomycin compared to placebo. Thus, there is a pharmacokinetic interaction, and the combination of triazolam and troleandomycin should be avoided or the dose of triazolam should be adjusted. The most likely mechanism is a diminished hepatic first-pass effect, and a decrease in the apparent oral clearance of triazolam.
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  • 70
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    European journal of clinical pharmacology 32 (1987), S. 577-582 
    ISSN: 1432-1041
    Keywords: yohimbine ; pharmacokinetics ; plasma levels ; renal elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetic disposition of yohimbine was examined in eight young male subjects following a single oral dose of 10 mg yohimbine hydrochloride. The drug was rapidly absorbed (absorption half-time 0.17±0.11 h) and rapidly eliminated from the plasma (elimination half-life 0.60±0.26 h). This clearance of yohimbine from plasma was constant over approximately 10 elimination half-lives, suggesting that distribution into a second pharmacokinetically distinct compartment was not responsible for the rapid decline in plasma yohimbine levels. Urinary excretion and the partitioning of the drug into red blood cells (RBC) was investigated. In the 24 h following oral administration of the drug, virtually no yohimbine was eliminated in the urine (0.35±0.50% of the administered dose). Furthermore, only 20% of blood-borne yohimbine was located in RBC. These results suggest that yohimbine is eliminated primarily through metabolism since the rapid plasma clearance of yohimbine was not the result of renal elimination or sequestration by RBC.
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  • 71
    ISSN: 1432-1041
    Keywords: moracizine·HCl ; antiarrhythmic ; ethmozine ; radiolabelled ; pharmacokinetics ; material balance ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Moracizine (ethmozine) is a phenothiazine derivative with demonstrated antiarrhythmic activity. To characterize the pharmacokinetics and material balance relationships in humans, we have given14C-moracizine·HCl as a single oral dose of 500 mg (50 μCi) to six healthy men. Plasma, urine, and faecal samples were collected for 7 days after administration and the concentrations of total radioactivity and intact moracizine were determined by liquid scintillation counting and HPLC, respectively. Urine and faecal recovery accounted for 95% of the administered radioactivity. Most of this radioactivity was found in the faeces (59%). Only 0.05% of the dose was recovered from urine as intact moracizine. The Cmax and AUC for moracizine equivalents of total radioactivity were 4- and 18-fold higher, respectively, than the corresponding values for intact moracizine. Additionally, both the disappearance of total radioactivity from plasma and its excretion rate into urine were slower in comparison to intact drug. Terminal t1/2 values calculated from plasma concentration-time data were 85.2 and 3.5 h for total radioactivity and intact moracizine, respectively. However, based on urinary excretion rates, the t1/2 for total radioactivity was shorter (29.3 h) while the t1/2 for intact drug was comparable (2.7 h) to the results obtained from the plasma data. The oral plasma clearance of moracizine was relatively large (2.2l·min−1), suggesting first-pass metabolism. The estimated oral systemic availability of moracizine was 34%.
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  • 72
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    European journal of clinical pharmacology 31 (1987), S. 711-714 
    ISSN: 1432-1041
    Keywords: flecainide ; pharmacokinetics ; moderate renal failure ; variability of elimination half-time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of flecainide after the oral administration of 100 mg to 8 patients without renal impairment and 8 patients with mild to moderate renal failure. Both groups gave comparable results with respect to the peak plasma concentrations and the time to peak. There was a significant correlation between renal flecainide clearance and endogenous creatinine clearance. The elimination half-time in the patients with impaired renal function was significantly longer (19.9, SD 9.9 h) than that in the patients with normal renal function (11.5, SD 4.2 h), but the variability in the elimination half-time in renal failure could not be explained on the basis of the available results.
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  • 73
    ISSN: 1432-1041
    Keywords: captopril ; uraemia ; captopril disulfide ; dialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have measured the plasma concentrations of captopril and total disulfide conjugates of captopril after a 50 mg oral dose in 6 uraemic patients on maintenance dialysis and in 8 hypertensive subjects with normal renal function. The mean peak plasma concentration of captopril was 2.5 times higher (0.447 µg·ml−1 vs 0.181 µg·ml−1) and the concentrations of the disulfides 4 times higher (3.62 µg·ml−1 vs 0.924 µg·ml−1) in the uraemic patients. Moreover captopril disulfide conjugates in the uraemic subjects reached peak concentrations at 8 h after the dose and subsequently felt. The apparent plasma half-time was 46±19 h. Only 15% of these conjugates were removed by dialysis. This marked accumulation of captopril conjugates was associated with a sustained fall in both systolic and diastolic blood pressures. In uraemic patients the mean maximum reduction in systolic and diastolic blood pressures were 37±7 mmHg and 24±9 mmHg respectively, occurring 6 h after the dose, compared with 8±7 and 8±1 mmHg respectively at 30 min in normal renal function patients. These results are consistent with the results of animal experiments, which show that captopril disulfides can be converted back to free captopril and can contribute to the antihypertensive effect of the drug. They provide a reationale for reducing the dose and frequency of administration of captopril in patients with significant renal impairment.
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  • 74
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    European journal of clinical pharmacology 32 (1987), S. 309-311 
    ISSN: 1432-1041
    Keywords: digoxin ; verapamil ; cirrhosis ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of a single low dose of verapamil (80 mg) on the serum levels of digoxin (single dose of 0.5 mg) was studied in 6 patients with hepatic cirrhosis and in 6 healthy volunteer controls. In the cirrhotic patients verapamil increased the peak serum level and the total AUC of digoxin by 98% and 32%, respectively. There was an associated 23% decrease in the renal digoxin clearance. In normal subjects only marginal alterations in digoxin kinetics were observed following verapamil administration. The results indicate that cirrhosis magnifies the influence of verapamil on digoxin kinetics.
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  • 75
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    European journal of clinical pharmacology 32 (1987), S. 303-307 
    ISSN: 1432-1041
    Keywords: azapropazone ; arthritis ; pharmacokinetics ; synovial fluid level ; synovial tissue level
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration-time curves of azapropazone in synovial fluid and tissues have been studied in arthritic patients after an i.v. bolus (600 mg) and under steady-state conditions. Synovial fluid and tissue samples were taken intraoperatively 0.45–60 h after administration. The azapropazone concentrations in synovial fluid, synovial tissue and plasma were correlated. The levels in synovial fluid were usually lower than corresponding plasma levels. Under steady-state conditions azapropazone did not accumulate in synovial tissues.
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  • 76
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    European journal of clinical pharmacology 32 (1987), S. 317-320 
    ISSN: 1432-1041
    Keywords: ranitidine ; amitriptyline ; drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of an interaction of ranitidine with amitriptyline was assessed by means of amitriptyline and nortriptyline plasma concentration measurements, blood pressure and pulse rate, digit symbol substitution, and visual analogue scales. Ranitidine had no effect on amitriptyline or nortriptyline concentrations. Responses recorded by the digit symbol substitution and visual analogue scale tests correlated with changes in concentrations of amitriptyline and nortriptyline in plasma. No effects on blood pressure or pulse rate were observed. We concluded that there was no effect of ranitidine on amitriptyline kinetics or response in the conditions of our study.
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  • 77
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    European journal of clinical pharmacology 32 (1987), S. 351-355 
    ISSN: 1432-1041
    Keywords: nifedipine ; cimetidine ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma pharmacokinetics of nifedipine and the formation of its metabolites have been studied in volunteers under conditions which would affect the activity of the cytochrome P-450 system. The pharmacokinetics of a 10-mg capsule of nifedipine were not significantly different between smokers and non-smokers of similar age. After pretreatment with cimetidine, which inhibits the activity of cytochrome P-450, the peak plasma concentration and area under the plasma-time concentration curve for nifedipine were increased by a mean 84%. In contrast, pre-treatment with ranitidine which has little effect on cytochrome P-450, did not significantly alter nifedipine pharmacokinetics. Smoking does not contribute significantly to the variability in nifedipine pharmacokinetics. However, the interaction between nifedipine and cimetidine, but not ranitidine, may be of clinical importance.
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  • 78
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    European journal of clinical pharmacology 32 (1987), S. 377-382 
    ISSN: 1432-1041
    Keywords: morphine ; renal failure ; pharmacokinetics ; morphine-3-glucuronide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of morphine and its glucuronidated metabolites were investigated in seven patients with advanced renal failure. The terminal elimination half life of morphine varied between 1.5 and 4.0 h (mean 2.4 h), the volume of distribution between 2.5 and 6.3 l·kg−1 (mean 4.4 l·kg−1) and the total plasma clearance between 13.3 and 31.3 l·min−1·kg−1 (mean 21.1 l·kg−1). There were no statistically significant differences between the pharmacokinetic data in the uraemic patients and in a control group of cancer patients with normal kidney function. The concentrations of the glucuronidated metabolites rapidly rose to levels above those of morphine. The elimination half-life of M3G varied between 14.5 and 118.8 h (mean 49.6 h) in the renal failure patients, which is distinctly different from the 2.4 to 6.7 h (mean 4.0 h) found in patients with normal kidney function. There was a significant correlation between the half-life of M3G and renal function estimated as serum urea. Thus, the metabolism of morphine in patients with kidney disease is not significantly impaired. The clinical importance of the high concentrations of glucuronides in uraemic patients is not known.
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  • 79
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    European journal of clinical pharmacology 32 (1987), S. 395-401 
    ISSN: 1432-1041
    Keywords: probenecid ; Michaelis-Menten kinetics ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six healthy volunteers were given probenecid 0.5, 1 and 2 g p.o. and 0.5 g i.v. The protein binding of probenecid at different concentrations in human plasma was estimated by equilibrium dialysis. The free fraction was found to increase nonlinearly with increasing total probenecid concentration, up to a maximum free fraction of 26%. The plasma concentration-time data after the oral doses were described by a one-compartment open model with first-order absorption and Michaelis-Menten elimination. The mean absorption rate constant 0.0072 min−1 was dose-independent, and the maximal rate of elimination (mean 1429 µg/min) did not differ between doses whether calculated from the total or free concentrations. The Michaelis-Menten constant decreased significantly from 67.1 to 55.5 µg/ml as the dose increased from 1 g to 2 g, while the unbound Michaelis-Menten constant remained unchanged. The elimination of probenecid after the 0.5 g dose was in the linear region of the Michaelis-Menten elimination when calculated from the total and the free concentrations. The volume of distribution increased only slightly from 9.5 to 11.4 l as the dose increased from 0.5 to 2 g, but the unbound volume of distribution decreased significantly from 164 to 99 l. Absorption was complete and was independent of the dose administered.
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  • 80
    ISSN: 1432-1041
    Keywords: adrenergic beta-receptors ; propranolol ; beta-blockade ; pharmacokinetics ; leukocyte beta-receptors ; leukocytes ; exercise tachycardia ; 4—OH-propranolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The chronotropic response to a single oral dose of propranolol in 23 healthy subjects has been related to the plasma propranolol concentration and the density of β-adrenoceptors on peripheral polymorphonuclear leucocytes. The percentage reduction in exercise-induced tachycardia was significantly correlated with the log plasma propranolol concentration within subjects but not between subjects. Taking the concentration of the active metabolite 4-hydroxypropranolol into account did not improve the interindividual correlation. The reduction in exercise-induced tachycardia was significantly correlated with the maximum binding density of (125I)-hydroxybenzylpindolol on polymorphonuclear leucocyte membrane fragments measured before medication. A response index (% reduction in exercise-induced tachycardia/plasma propranolol concentration) was correlated with the maximum binding density of (125I)-hydroxybenzylpindolol (predrug) at 2 h (rs=0.72), 4 h (rs=0.84) and 6 h (rs=0.73) after dosing. The data suggest that interindividual variation in the response to propranolol after a single oral dose is determined by interindividual differences both in plasma propranolol and adrenoceptor density.
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  • 81
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    European journal of clinical pharmacology 31 (1987), S. 695-699 
    ISSN: 1432-1041
    Keywords: doxorubicin ; sarcoma ; pharmacokinetics ; polychemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of doxorubicin has been studied in 26 sarcoma patients receiving polychemotherapy. Mean elimination half-life was 34.7±16.6 h and the total plasma clearance was 29.5±9.31·h−1·m−2. No relationship was found between the pharmacokinetic parameters and the response to treatment, or its toxicity. Special attention was paid to the early-phase kinetics of the drug (3–20 min after injection). A correlation between the early clearance and the ages of the patients was observed. The early clearance was clearly correlated with the total plasma clearance measured over 48 h after injection, indicating the importance of the distribution phase in the overall kinetics of the drug.
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  • 82
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    European journal of clinical pharmacology 31 (1987), S. 701-704 
    ISSN: 1432-1041
    Keywords: theophylline ; miocamycin ; drug interaction ; metabolism ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction between a new macrolide antibiotic, miocamycin, and theophylline was evaluated in a single cross-over study in 5 asthmatic children. Each patient received a single dose of theophylline (4.3 mg/kg) delivered in 15 min using a constant-rate infusion pump, immediately before and after a 10 day course of miocamycin 17.5 mg/kg b.d. The pharmacokinetics of theophylline were calculated for each phase of the study. The elimination rate constant (3.92 vs 3.74 h−1), the mean total body clearance (1.71 vs 1.8 ml·min·kg−1) and the mean apparent volume of distribution (0.57 vs 0.58 l·kg−1) did not differ. The result can be explained by the inability of the antibiotic to form inactive cytochrome P-450 metabolite complexes which can interfere with the metabolism of theophylline. Thus, miocamycin can safely be administered to asthmatic children requiring theophylline treatment, when they have an infection due to susceptible pathogens.
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  • 83
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    European journal of clinical pharmacology 31 (1987), S. 733-736 
    ISSN: 1432-1041
    Keywords: meptazinol ; pharmacokinetics ; elderly patients ; healthy volunteers ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have determined the pharmacokinetics of meptazinol after its intravenous and intramuscular administration in a crossover study in 7 elderly hospital in-patients (〉70 years), and have compared with the results from 14 healthy, young volunteers (ages 20–40 years). The systemic availability after i.m. administration was comparable to that after i.v. administration, a result consistent with the physicochemical properties of the drug. There was a slight, but statistically significant (p〈0.01) prolongation in t1/2z in the elderly (mean 2.93 h) compared with the young (mean 2.06 h). This was associated with a 25% lower clearance in the elderly rather than with any alteration in volume of distribution. However, these changes would not appear to be substantial enough to require a revised dosage recommendation for meptazinol for this age group.
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  • 84
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    European journal of clinical pharmacology 31 (1987), S. 743-743 
    ISSN: 1432-1041
    Keywords: chloroquine ; dose dependence ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 85
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    European journal of clinical pharmacology 32 (1987), S. 17-22 
    ISSN: 1432-1041
    Keywords: felodipine ; calcium antagonist ; normal man ; renal function ; albumin excretion ; beta2-microglobulin excretion ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute renal effects of a single oral dose of felodipine 0.15 mg/kg were studied in 8 healthy males. Thirty minutes after administration the mean plasma concentration was 25.7 nmol/l. There was a significant reduction in diastolic blood pressure (24%) and a concomitant rise in heart rate (38%), leaving the systolic pressure unchanged. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique using the clearance of125I-iothalamate and131I-hippuran respectively. GFR was unchanged and the filtration fraction (FF) was reduced, whilst there was a decrease in renal vascular resistance (RVR). The glomerular filter characteristics were unchanged, as estimated by the unchanged excretion rate of albumin. There was a significant rise in the clearance of sodium (176%) but only a small and insignificant increase in urine volume. Clearance of potassium was decreased. An increase in the clearance of uric acid and a rise in the beta-2-microglobulin excretion rate were found, both suggesting a proximal tubular effect of felodipine. The excretion rate of calcium was increased.
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  • 86
    ISSN: 1432-1041
    Keywords: atenolol ; amiloride ; hydrochlorothiazide ; young ; elderly ; pharmacokinetics ; pharmacodynamics ; volunteers ; patients ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six normal young and six normal elderly volunteers and six elderly hypertensive patients took part in an acute and chronic dose study of a combination capsule containing atenolol (50 mg), hydrochlorothiazide (25 mg) and amiloride (2.5 mg) designed for the treatment of hypertension. No difference in any of the drug pharmacokinetic parameters could be detected between the hypertensives and the normal elderly subjects. The bio-availability and the 24-h blood concentrations of all three drugs, half-life of atenolol and amiloride and the peak concentration of hydrochlorothiazide was significantly greater in the elderly. The 24-h blood concentrations of atenolol and hydrochlorothiazide did not alter with chronic dosing, but amiloride concentrations were significantly higher at this time in all groups. A significant fall in the blood pressure was observed in the hypertensive group. Heart rate fell more in the normal and hypertensive elderly subjects than in the young. The combination has shown to be an effective and well tolerated antihypertensive in the elderly patient with a 24-h duration of action.
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  • 87
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    European journal of clinical pharmacology 32 (1987), S. 165-172 
    ISSN: 1432-1041
    Keywords: warfarin ; cimetidine ; ranitidine ; stereochemistry ; drug-drug interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Stereochemical aspects of the potential interaction between the oral anticoagulant warfarin and the H2-antagonists, cimetidine and ranitidine, were investigated. A single 25 mg oral dose of racemic warfarin was administered on Day 4 of a randomised 9-day multiple dosing regimen of either cimetidine (800 mg o.d.) ranitidine (300 mg o.d.) or placebo. The degree of anticoagulation produced by warfarin was quantificated by the determination of both the prothrombin and Factor VII clotting times. Ranitidine had no effect on the pharmacodynamics of warfarin or the pharmacokinetics of the individual warfarin enantiomers. Cimetidine whilst producing no statistically significant change in the pharmacodynamics of warfarin or in the pharmacokinetics of the pharmacologically more potent (S) enantiomer, did produce a statistically significant decrease in the clearance of the (R) enantiomer, possibly due to metabolic inhibition of this species.
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  • 88
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    European journal of clinical pharmacology 32 (1987), S. 357-360 
    ISSN: 1432-1041
    Keywords: nitrendipine ; food intake ; pharmacokinetics ; variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of nitrendipine were measured, after single (20 mg) oral doses, in young healthy volunteers. On three occasions the subjects ingested the dose having fasted overnight. Data from these three occasions were used to assess variability in nitrendipine pharmacokinetics and both inter- and intra-subject variability were high. On a fourth occasion, the subjects took the tablet after a standard meal. The effects of food on nitrendipine pharmacokinetics, based on the comparison of data from the first fasting visit and the food visit, were negligible.
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  • 89
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    European journal of clinical pharmacology 32 (1987), S. 583-586 
    ISSN: 1432-1041
    Keywords: tiapride ; Huntington's disease ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic properties of a single oral dose of 100 mg of tiapride were studied in six patients with Huntington's disease. The results for five patients were consistent with a two compartment open model. Peak plasma concentrations were observed within 2 h following durg administration with a mean value of 0.92 μg/ml being recorded. The drug was rapidly eliminated as unmetabolised tiapride in the urine, 51% of the dose was recovered in 24 h. The plasma elimination half-life was 5.3 h and the average apparent plasma clearance was 16.6 l/h.
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  • 90
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    European journal of clinical pharmacology 32 (1987), S. 593-596 
    ISSN: 1432-1041
    Keywords: dexamethasone ; dexamethasone phosphate, antiemetic ; pharmacokinetics ; cancer chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or doxorubicin. The patients received graded doses of dexamethasone phosphate, in the range 40–200 mg, dependent upon nausea and vomiting scores, during up to three consecutive cycles of cancer chemotherapy. Plasma and urine concentrations of dexamethasone (dexamethasone alcohol) were measured by HPLC. The plasma concentration-time data were described by an open two-compartment model. The pharmacokinetic variables were independent of the dose of dexamethasone over the range studied. The terminal half-time was 4.0±0.4 h and the total body clearance was 3.5±0.4 ml·min−1·kg−1. The volume of the central compartment and the total apparent volume of distribution were 0.23±0.03 and 1.0±0.1 l·kg−1 respectively. Approximately 8% of the dose was excreted into the urine as dexamethasone.
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  • 91
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    European journal of clinical pharmacology 31 (1987), S. 617-619 
    ISSN: 1432-1041
    Keywords: chronopharmacology ; indomethacin ; suppository ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of a single 100 mg indomethacin suppository were studied in 12 healthy volunteers on two occasions at least 7 days apart. Suppositories were administered in randomised order at 9.00 and 21.00 hours to see if there was evidence of a diurnal variation in kinetic parameters. The study failed to show a significant change in single dose kinetics with the time of suppository administration. This is in contrast to previous work [1] demonstrating a circadian rhythm in the kinetics of a single oral dose of indomethacin. This suggests that the chronopharmacokinetics of indomethacin is dependent on the function of the upper gastrointestinal tract.
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  • 92
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    European journal of clinical pharmacology 31 (1987), S. 625-627 
    ISSN: 1432-1041
    Keywords: verapamil ; breast milk ; norverapamil ; breast feeding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentrations of verapamil and norverapamil have been measured in milk and plasma samples from a 32year-old woman treated with verapamil 80 mg tds while breast-feeding her child. The average steady-state concentrations of verapamil and norverapamil in milk were, respectively, 60% and 16% of the concentrations in plasma. The breast-fed child received less than 0.01% of the dose of verapamil given to the mother. No verapamil or norverapamil (〈1 ng/ml) could be detected in the plasma from the child.
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  • 93
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    European journal of clinical pharmacology 31 (1987), S. 575-578 
    ISSN: 1432-1041
    Keywords: felodipine ; metoprolol ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This double-blind, cross-over study in healthy male subjects evaluated the pharmacokinetics of felodipine and metoprolol given both separately and in combination. During three, five-day study periods, felodipine 10 mg b.d., metoprolol 100 mg b.d. and a combination of the two, were given in random order. There was at least a 7-day washout period between each pharmacokinetic study day. Plasma levels of unchanged felodipine and metoprolol were measured for 24 h after the last dose, on the 5th day of each treatment period. Eight subjects, aged 19–22 years, completed the study. Both felodipine and metoprolol, given alone and in combination, were well tolerated. None of the felodipine pharmacokinetic variables (tmax, Cmax, Cmin, AUC (0–12) and t1/2) changed significantly when felodipine and metoprolol were given in combination. Cmax and AUC (0–12) for metoprolol increased significantly when metoprolol and felodipine were combined, although tmax, Cmin and t1/2 for metoprolol remained unchanged. The changes in metoprolol pharmacokinetics induced by felodipine are small and unlikely to be clinically important.
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  • 94
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    European journal of clinical pharmacology 31 (1987), S. 583-588 
    ISSN: 1432-1041
    Keywords: cotinine ; pharmacokinetics ; non-smokers ; absolute bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Cotinine, the main metabolite of nicotine, was administered intravenously to healthy male non-smoking volunteers in doses of 5, 10 and 20 mg, and orally in doses of 10 and 20 mg. Intravenous administration was characterized by a dose-independent half-life of 12.2 h, mean residence time of 15.9 h, total clearance of 3.64 l h−1 and a volume of distribution of 56.5 l. Renal clearance was 0.46 l h−1 and approximately 12.0% of the dose was excreted unchanged in the urine. The mean absorption time after oral dosing ranged between 1 and 3 h, the peak concentration was reached within 45 min and the mean elimination half-lives were 12.9 and 11.7 h, respectively, after the 10 and 20 mg doses. Systemic bioavailability ranged between 0.84 and 1.11 following 10 mg and between 0.97 and 1.03 following the 20 mg dose. Mean urinary recovery and renal clearance were almost identical with the values after iv administration.
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  • 95
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    European journal of clinical pharmacology 31 (1987), S. 595-600 
    ISSN: 1432-1041
    Keywords: caffeine ; exercise ; obesity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of obesity, exercise, and the interaction of obesity and exercise were examined in 6 caffeine naive, untrained, nonsmoking, college males (3 lean (LV), 3 obese (OV)). Each subject received caffeine (oral, 5.83 mg·kg−1 lean body weight) or placebo (50 mg citrate) prior to 3 h of seated rest and prior to 90 min of treadmill walking (40% of their maximal aerobic power) followed by 90 min of seated recovery. Serum samples were collected at various times and analyzed for caffeine by HPLC. Pharmacokinetic analysis indicated that at rest, OV had a significantly higher absorption rate constant (Ka 0.0757 vs. 0.0397 min−1), lower elimination rate constant (Ke 0.0027 vs. 0.0045 min−1), and longer serum half-life (t1/2 4.37 vs. 2.59 h) in comparison to LV. In exercise, as well as at rest LV and OV had a large difference in the volume of distribution (43.2 vs. 101. 1) (rest, 54.1 vs. 103.1). Exercise consistently resulted in a decrease in the maximal serum concentration of caffeine and the area under the curve in OV while having no consistent effect on LV. The interactive effects of obesity and exercise could not be dissociated. However, these results demonstrate that both obesity and exercise have modified the pharmacokinetics of caffeine.
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  • 96
    ISSN: 1432-1041
    Keywords: dextran ; hydroxyethylstarch ; haemodilution ; ischaemic stroke ; plasma viscosity ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 21 patients with ischaemic strokes we have monitored plasma viscosity, total plasma concentration, numeric average molecular weight (Mn), and weight average molecular weight (Mw) of Dextran 40 (dextran) and hydroxyethylstarch 200/0.5 (HES) during 10 days of treatment (days 1–4, 2×500 ml; days 5–10, 1×500 ml). Plasma concentrations of dextran increased during the first 4 days (8.3 mg·ml−1 on the first day to 18.0 mg·ml−1 on the fifth day), reached an apparent steady state of 17.2 mg·ml−1 during the next 6 days, and declined subsequently with a half-time (t1/2) of 4.03 days. After ten days treatment Mn and Mw were shifted towards higher values. Plasma viscosity increased from 1.26 mPas to 1.69 mPas on Day 10 (p〈0.01) and was linearly correlated with the total plasma concentration of dextran (p〈0.001; r=0.88). Total plasma concentrations of HES averaged 11.7 mg·ml−1 on Day 1 and 12.4 mg·ml−1 on Day 5. The molecular weight distribution did not change during the infusions but decreased in comparison with the administered solution. Plasma viscosity fell from 1.40 mPas to 1.30 mPas at Day 10 (p〈0.05) and was not related to the concentration of HES. The haemodiluting effect, as indicated by a decrease of the haematocrit, was 22% and 16.8% for dextran and HES respectively. These data suggest several advantages of HES compared with dextran in haemodilution therapy of ischaemic stroke.
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  • 97
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    European journal of clinical pharmacology 31 (1987), S. 569-573 
    ISSN: 1432-1041
    Keywords: tolazoline ; neonates ; persistent fetal circulation ; pharmacodynamic effects ; pharmacokinetics ; pulmonary circulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of two doses of tolazoline have been compared in 2 groups of newborns suffering from the persistent fetal circulation syndrome. The effects on PaO2 and AaDO2 were similar in the 2 groups who received either a bolus of 1 or 0.5 mg·kg−1 tolazoline, followed by a continuous infusion of 1 or 0.5 mg·kg−1·h−1. The observed changes did not differ significantly from those previously observed in babies treated with 2 mg·kg−1. A rise in PaO2 and a reduction in AaDO2 were usually observed shortly after the bolus injection and at plasma levels between 1.5 and 4 µg·ml·−1. A progressive rise in plasma level over time occurred after 1 mg·kg−1 (and in the previous study of 2 mg) but not with 0.5g/kg tolazoline. The elimination half-life of tolazoline in 6 patients was 5 to 13 h. The data suggest that continuous infusion of tolazoline is not necessarily required and that the dose of 0.5 mg/kg is more appropriate and safer than the higher doses usually proposed.
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  • 98
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    European journal of clinical pharmacology 32 (1987), S. 67-70 
    ISSN: 1432-1041
    Keywords: enprofylline ; pharmacokinetics ; elderly ; renal excretion ; half-life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of enprofylline, a new potent antiasthmatic, has been studied in 20 healthy, elderly subjects, aged 65 to 81 years, and in 7 young adult controls, aged 23 to 37 years. The dose of 1 mg/kg body weight was given as an i.v. infusion. Plasma levels of enprofylline were followed for about 7 h and urine levels for 24 h. Both groups eliminated the major portion of the dose (about 83%) by renal excretion. As expected the mean creatinine clearance (92.5 ml·min−1· 1.73 m−2) was moderately decreased in the elderly subjects. The total clearance of enprofylline was 0.16 1·h−1·kg−1 and the renal clearance was 0.13 l·h−1·kg−1, which was significantly lower than that in the young controls (0.28 and 0.22 l·h−1·kg−1) respectively. Thus, the enprofylline clearance had fallen relatively more (about 40%) than the decrease in creatinine clearance (about 20%) with age. The half-life of enprofylline in old age was 2.5 h, which was significantly longer than in the younger adults (1.8 h). It is concluded that the pharmacokinetics of enprofylline was significantly influenced by advanced age, mainly due to reduced renal excretion. This reduction was more pronounced than anticipated from the age-dependent decline in creatinine clearance.
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  • 99
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    European journal of clinical pharmacology 32 (1987), S. 103-106 
    ISSN: 1432-1041
    Keywords: fenoldopam ; peripheral dopamine agonist ; pharmacokinetics ; absorption ; food effects ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eight healthy volunteers participated in an open crossover study to assess the effect of a standardised meal on the systemic availability of a single oral dose of fenoldopam mesylate 100 mg. Subjects were studied on four separate occasions, twice fasting and twice fed in randomised, balanced order. Plasma and urine samples were obtained before and at regular intervals up to 25 h post dose. Measurement of fenoldopam (SK&F 82526) and its 8-sulphate metabolite (SK&F 87782) were by means of HPLC-EC analysis. Area under the plasma concentration time curve (AUC) and maximum detected plasma concentration (Cmax) for fenoldopam and SK&F 87782 were significantly reduced whereas time to maximum concentration was significantly increased with food. Using AUC's for fenoldopam and SK&F 87782, mean relative bioavailabilities were 35% and 81% respectively under fed compared with fasting conditions. Twenty-four hour excretion of fenoldopam was significantly reduced with food, but excretion of SK&F 87782 was apparently unchanged. Mean relative bioavailabilities calculated from these data were 83% and 86% respectively. Relatively large inter-subject variability in AUC and Cmax were seen, but intra-subject variability was not marked. Mild symptoms associated with vasodilation were reported on all study days.
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  • 100
    ISSN: 1432-1041
    Keywords: mefloquine ; mefloquine/sulphadoxine/pyrimethamine ; Thai subjects ; pharmacokinetics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of mefloquine were studied in 12 healthy Thai male and 12 healthy Thai female volunteers. Mefloquine (MQ) was administered either alone (750 mg orally) or in combination (MSP) with sulphadoxine (1.5 g) and pyrimethamine (75 mg) to each of 6 male and 6 female subjects. Plasma concentrations of MQ were measured by HPLC at intervals for 42 days. There was considerable interindividual variability in the pharmacokinetic parameters; for example in the male subjects receiving MQ alone peak concentrations ranged between 638 and 2494 ng·ml−1 with a mean concentration of 1442 ng·ml−1. Compared to previously published data on MQ concentrations in Caucasian male subjects, the present study indicates that higher concentrations are achieved in Thai subjects. The only significant difference in kinetic parameters between male and female subjects receiving MQ alone was in the mean residence time (MRT) which was greater in females. However, an analysis of pharmacokinetic parameters following administration of the combination preparation showed that the time to peak (tmax) was significantly reduced in females receiving MSP compared to the corresponding females given MQ alone and males given MSP. When data obtained from all subjects (male and female) receiving either MQ alone or MSP were combined, both MRT and half-life were significantly greater in subjects given MSP. There is therefore some evidence that therapeutic concentrations of MQ are maintained for a longer period of time following MSP administration.
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