Reduction of Steady-State Valproate Levels by Other Antiepileptic Drugs

Steady-state plasma valproate (VPA) levels were analyzed in 37 children after 6 weeks of VPA therapy. Twenty-six patients were receiving other antiepileptic drugs in addition to VPA (experimental group). Eleven patients who received VPA alone served as controls. The mean VPA dose was not statistically different for the two groups (experimental group, 35.4 mg/kg/ day, 11.6 SD; control group, 31.1 mg/kg/day, SD 6.6) The mean plasma VPA level was significantly lower for the experimental group (63.0 Μg/m1, SD 21.8) than for the control (99.3 Μg/m1), SD 23.3) ( p < 0.01). VPA levelrdose ratio (LDR) was also reduced in the experimental group (1.92, SD 0.75) as compared to controls (3.26, SD 0.65) ( p < 0.01). Within the experimental group the VPA levels and VPA LDR were significantly reduced in patients receiving either phenytoin or phenobarbital. The data suggest that other antiepileptic drugs significantly alter the steady-state level to dose relationship for VPA. RÉSUMÉ Le taux plasmatique À l'Équilibre du valproate de sodium (VPA) a ÉtÉÉtudiÉ chez 37 enfants aprÈs 6 semaines de thÉrapeutique. Vingt six patients reÇoivent d'autres mÉdicaments antiÉpileptiques associÉs au VPA (groupe expÉrimental) alors que 11 sujets tÉmoins ne reÇoivent que le VPA seul. La posologie moyenne du VPA n'est pas significativement diffÉrente entre les deux groupes (35,4 mg/kg/jour ± 11,6 centre 31,1 mg/kg/jour ± 6,6). Le taux plasmatique de VPA est significativement plus bas dans le groupe experimental (63,0 Μg/ml ± 21,8) contre 99,3 Μg/ml ± 23,3 dans le groupe tÉmoin ( p < 0,01). Le rapport taux plasmatique/posologie (LDR) a ÉtÉ diminuÉ dans le groupe expÉrimental (1,92 ± 0,75) par rapport au groupe tÉmoin (3,26 ± 0,65), p < 0,01 en particulier chez les malades recevant de la phÉnytoÏne ou du phÉnobarbital. La posologie moyenne du VPA n'Étant pas significativement diffÉrente dans les deux groupes, les faits observÉs suggÈrent que l'addition d'autres antiÉpileptiques est capable de modifier le taux À l'Équilibre du VPA plasmatique en fonction de la dose administrÉe. RESUMEN Se analizaron los niveles estables de valproato en plasma (VPA) en 37 niÑos despuÉs de 6 semanas de terapia con VPA. Ventiseis pacientes recibÍan otros fÁrmacos ademÁs de VPA (grupo experimental) y once sÓlo tomaban VPA y sirvieron como controles. La dosis media de VPA no fue significativamente distinta en los dos grupos (grupo experimental: 35,4 mg/kg/dÍa, DS 11,6; grupo control: 31.1 mg/kg/dÍa, DS 6,6). El nivel plasmÁtico medio de VPA fue significativamente inferior en el grupo experimental (63,0 Μg/ml, DS 21,8) que en el control (99,3 Μg/ml, DS 23,3), p < 0,01. La relaciÓn nivel de VPA: dosis (LDR) estaba tambiÉn reducida en el grupo experimental (1,92, DS 0,75) al compararla con los controles (3,26, DS 0,65), p < 0,01. Dentro del grupo experimental los niveles de VPA y la LDR estaban significativamente reducidos en pacientes que tomaban fenitoÍna o fenobarbital. La dosis media no fue diferente entre los grupos experimental y control. Estos datos sugieren que la ingestiÓn de otros fÁrmacos alteran de modo significativo los niveles estables de VPA en relaciÓn con la dosis. ZUSAMMENFASSUNG In steady-state befindliche Plasma Valproatspiegel (VPA) wurden bei 37 Kindern nach 6 wÖchiger VPA-Therapie analysiert. 26 Patienten erhielten zusÄtzlich zum VPA andere Antiepileptika (experimentelle Gruppe). 11 Patienten, die VPA alleine bekamen, dienten als Kontrollen. Die mittlere VPA-Dosis war in beiden Gruppen nicht signifikant Vunterschiedlich (experimentelle Gruppe 35,4 mg/kg pro Tag, 11,6 SD; Kontrollgruppe 31,1 mg/kg pro Tag, SD 6,6). Der mittlere Plasma VPA-Spiegel war signifikant niedriger in der experimentellen Gruppe (63,0 Μg/ml, SD 21,8) als in der Kontrollgruppe (99,3 Μg/m1, SD 23,3), p < 0.01. Das VerhÄltnis VPA-Spiegel: Dosis (LDR) war in der experimentellen Gruppe ebenfalls reduziert (1,92, SD 0,75) gegenuber der Kontrollgruppe (3,26, SD 0,65), p < 0.01. Innerhalb der experimentellen Gruppe waren die VPA-Spiegel und die VPA/LDR bei Patienten, die entweder Phenytoin oder Phenobarbital bekamen, signifikant erniedrigt. Die mittlere VPA-Dosis war nicht signifikant unterschiedlich in der experimentellen und in der Kontrollgruppe. Diese Daten lassen vermuten, daß andere Antiepileptika signifikanterweise den Steady-state-Spiegel im Hinblick auf die verabfolgte Dosis VPA Ändern.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66058/1/j.1528-1157.1981.tb06154.x.pd

Collusion through Joint R&D: An Empirical Assessment

This paper tests whether upstream R&D cooperation leads to downstream collusion. We consider an oligopolistic setting where firms enter in research joint ventures (RJVs) to lower production costs or coordinate on collusion in the product market. We show that a sufficient condition for identifying collusive behavior is a decline in the market share of RJV-participating firms, which is also necessary and sufficient for a decrease in consumer welfare. Using information from the US National Cooperation Research Act, we estimate a market share equation correcting for the endogeneity of RJV participation and R&D expenditures. We find robust evidence that large networks between direct competitors – created through firms being members in several RJVs at the same time – are conducive to collusive outcomes in the product market which reduce consumer welfare. By contrast, RJVs among non-competitors are efficiency enhancing

The Wage Premium of Globalization: Evidence from European Mergers and Acquisitions

We provide evidence on the impact of globalization on labor market outcomes analyzing pay differences between foreign-acquired and domestically-owned firms. For this purpose, we use firm level data from 16 European countries over the time period 1999-2006. Applying propensity score matching techniques we estimate positive wage premia of cross-boarder merger and acquisitions (M&As), suggesting that foreign acquired firms exhibit higher short-run (post-acquisition) wages than their domestic counterparts. The observed wage disparities are most pronounced for low paying firms (with average wages below the median). Finally, we find systematic wage premia in Western European countries, but not so in Eastern Europe

Taxes and the Valuation of Dividends: A Study of Dividend Announcements in Germany

This paper investigates the impact of the 2001 tax reform in Germany on dividend announcement returns. With this major tax reform, the full imputation system was replaced by the half-income system, which had a significant impact on the relative taxation of dividends and capital gains for most investor classes. In an event study framework, we separate the tax effect of dividends from their positive signaling and agency cost effects to offer a more comprehensive picture of the valuation implications of dividends in Germany. Controlling for signaling and agency cost effects of dividends we find that the market response to positive dividend surprises is more pronounced under the full imputation system, where dividends are generally more favorable to investors from a tax perspective, than under the half-income system. Our results suggest that the observed decline in the dividend response coefficient is synchronized with the 2001 tax reform and hence attributable to the 2001 tax reform

Mergers and Acquisitions in Latin America: Industrial Productivity and Corporate Governance

This paper examines the impact of industrial productivity on transnationals M&As from OECD countries towards Latin American countries in the period 1996 to 2010. It also analyzes the relationship between external mechanism of corporate governance and transnational M&As. For this purpose we use a gravitational model at the industry level. We find that industry productivity and higher standards of corporate governance in the country of origin promote transnational M&As activity. However, it is also found that higher levels of capital and technological productivity decreases transnational M&As activity

Chinese multinationals: host country factors and foreign direct investment location

The study of Chinese multinationals (MNEs) is becoming one of the most promising research topics in the international business literature. After outlining the distinctive characteristics of the internationalization process of Chinese MNEs, this chapter analyzes the influence of various host country factors on the location of Chinese outward foreign direct investment (FDI). From a sample of 189 outward FDI decisions made by 35 mainland Chinese firms in 63 countries, our results show that host market size and the existence of overseas Chinese in the host country are positively associated with the number of Chinese FDIs. However, greater difficulty in doing business and host country political risk have no effect