Effects of Cytochrome P450 Enzyme Inhibitors on the Pharmacokinetics of Nonsteroidal Anti-inflammatory Drugs and Venlafaxine

Cytochrome P450 (CYP) enzymes play a pivotal role in the metabolism of many drugs. Inhibition of CYP enzymes usually increases the plasma concentrations of their substrate drugs and can thus alter the safety and efficacy of these drugs. The metabolism of many widely used nonsteroidal antiinflammatory drugs (NSAIDs) as well as the metabolism of the antidepressant venlafaxine is nown to be catalyzed by CYP enzymes. In the present studies, the effect of CYP inhibition on the armacokinetics and pharmacodynamics of NSAIDs and venlafaxine was studied in clinical trials with healthy volunteers and with a crossover design, by using different antifungal agents as CYP inhibitors. The results of these studies demonstrate that the inhibition of CYP enzymes leads to increased concentrations of NSAIDs. In most cases, the exposure to ibuprofen, diclofenac, etoricoxib, and meloxicam was increased 1.5to 2 fold when they were used concomitantly with antifungal agents. CYP2D6 inhibitor, terbinafine, substantially increased the concentration of parent venlafaxine, whereas the concentration of active moiety of venlafaxine (parent drug plus active metabolite) was only slightly increased. Voriconazole, an inhibitor of the minor metabolic pathway of venlafaxine, produced only minor changes in the pharmacokinetics of venlafaxine. These studies show that an evident increase in the concentrations of NSAIDs may be expected, if they are used concomitantly with CYP inhibitors. However, as NSAIDs are generally well tolerated, use of single doses of NSAIDs concomitantly with CYP inhibitors is not likely to adversely affect patient safety, whereas clinical relevance of longterm concomitant use of NSAIDs with CYP inhibitors needs further investigation. CYP2D6 inhibitors considerably affect the pharmacokinetics of venlafaxine, but the clinical significance of this interaction remains unclear.

V. A. Koskenniemen kokoelma

Kirjallisuuden professori V. A. Koskenniemen (1885-1962) kirjakokoelma säilytetään erillisenä kokoelmana Turun yliopiston pääkirjaston Koskenniemi-huoneessa. Kokoelmaan kuuluu n. 2800 nidettä, suurin osa kaunokirjallisuutta, erityisesti suomalainen lyriikka, kirjallisuudentutkimusta ja estetiikka. Kokoelmassa on runsaasti omistuskirjoituksia V. A. Koskenniemelle. Kokoelmassa on myös 10 kpl. V. A. Koskenniemen omaa käsikirjoitusta sidottuina. (käsikirjoitusliuskat sidottu kirjoiksi): Elegioja ynnä muita runoja. Teoksen käsikirjoitus. 120 s., Ilm. Kootut teokset I. Porvoo 1955, s. 145-243; Hannu. Erään nuoruuden runoelma. Teoksen käsikirjoitus. 73 s., ilm. WSOY, Porvoo 1913; Hiilivalkea. Teoksen käsikirjoitus. 57 s., Ilm. Kootut teokset I. Porvoo 1955, s. 93-144; Kevätilta Quartier Latinissa. Parisin muistelmia. Teoksen käsikirjoitus. 210 s., Ilm. Kootut teokset V. Porvoo 1955, s. 5-51; Konsuli Brennerin jälkikesä. Romaani. Teoksen käsikirjoitus. 259 s., Ilm. Kootut teokset IV. Porvoo 1955, s. 5-161; Lyyra ja paimenhuilu. Runosuomennoksia. Teoksen käsikirjoitus. 109 s., Ilm. Kootut teokset II. Porvoo 1955, s. 303-362; Nuori Anssi. Teoksen käsikirjoitus. 28 s., Ilm. nimellä Nuori Anssi Porvoo 1918 ja Kootut teokset II. Porvoo 1955, s. 283-301; Runon kaupunkeja ynnä muita kirjoitelmia. Teoksen käsikirjoitus. 330 s., Ilm. Kootut teokset V Porvoo 1955, s. 53-155; Sydän ja kuolema. Elegioja, lauluja ja epitaafeja. Teoksen käsikirjoitus. 105 s., Ilm. Kootut teokset I. Porvoo 1955, s. 203-243; Uusia runoja. Teoksen käsikirjoitus. 146 s., Ilm. Kootut teokset I, Porvoo 1955, s. 245-309. Kokoelma on osittain luetteloimaton, melkein 1300 nidettä löytyy Volter-tietokannasta.

Aspekteja [Peltoniemen Hintrikin surumarssista, Jousikvartetto nro 3 op. 19]

Soitinnus: viulut (2), alttoviulu, sello.

Stråkkvartett op. 122

Digitoitu 3. 10. 2007.

Pianokvintett op. 44

Digitoitu 3. 10. 2007.

Stråkkvartett Ess-dur (1930)

Digitoitu 3. 10. 2007.

Formal Power Analysis of Systems-on-Chip

The design methods and languages targeted to modern System-on-Chip designs are facing tremendous pressure of the ever-increasing complexity, power, and speed requirements. To estimate any of these three metrics, there is a trade-off between accuracy and abstraction level of detail in which a system under design is analyzed. The more detailed the description, the more accurate the simulation will be, but, on the other hand, the more time consuming it will be. Moreover, a designer wants to make decisions as early as possible in the design flow to avoid costly design backtracking. To answer the challenges posed upon System-on-chip designs, this thesis introduces a formal, power aware framework, its development methods, and methods to constraint and analyze power consumption of the system under design. This thesis discusses on power analysis of synchronous and asynchronous systems not forgetting the communication aspects of these systems. The presented framework is built upon the Timed Action System formalism, which offer an environment to analyze and constraint the functional and temporal behavior of the system at high abstraction level. Furthermore, due to the complexity of System-on-Chip designs, the possibility to abstract unnecessary implementation details at higher abstraction levels is an essential part of the introduced design framework. With the encapsulation and abstraction techniques incorporated with the procedure based communication allows a designer to use the presented power aware framework in modeling these large scale systems. The introduced techniques also enable one to subdivide the development of communication and computation into own tasks. This property is taken into account in the power analysis part as well. Furthermore, the presented framework is developed in a way that it can be used throughout the design project. In other words, a designer is able to model and analyze systems from an abstract specification down to an implementable specification.