A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion

Objective Levodopa in presence of decarboxylase inhibitors is following two-compartment kinetics and its effect is typically modelled using sigmoid Emax models. Pharmacokinetic modelling of the absorption phase of oral distributions is problematic because of irregular gastric emptying. The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Methods The modelling involved pooling data from two studies and fixing some parameters to values found in literature (Chan et al. J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):307-31). The first study involved 12 patients on 3 occasions and is described in Nyholm et al. Clinical Neuropharmacology 2003:26:156-63. The second study, PEDAL, involved 3 patients on 2 occasions. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function from video recordings on a treatment response scale between -3 and 3, where -3 represents severe parkinsonism and 3 represents severe dyskinesia.) were repeatedly collected until the clinical effect was back at baseline. At this point, the usual infusion rate was started and sampling continued for another two hours. Different structural absorption models and effect models were evaluated using the value of the objective function in the NONMEM package. Population mean parameter values, standard error of estimates (SE) and if possible, interindividual/interoccasion variability (IIV/IOV) were estimated. Results Our results indicate that Duodopa absorption can be modelled with an absorption compartment with an added bioavailability fraction and a lag time. The most successful effect model was of sigmoid Emax type with a steep Hill coefficient and an effect compartment delay. Estimated parameter values are presented in the table. Conclusions The absorption and effect models were reasonably successful in fitting observed data and can be used in simulation experiments.

Sports and mediatization : a case of women´s ski-jumping

Ski jumping was the only sport included in the Winter Olympics, where women were not allowed to take part until the first week of April 2011, when IOC decided to let them in to the Olympic family, a major victory for women´s ski-jumping. Since 2004 the Norwegian media had women ski jumping as one important topic in their media coverage. The third of March 2010 the new Holmenkollen ski-jumping hill was inaugurated. It had been rebuilt for the World Championships 2011. The first jump on the hill was surrounded by an intense debate. Annette Sagen was decided to be the first jumper on the hill after a poll on the social media channel Facebook that gave Annette Sagen over 40 000 votes.  However Tuesday the second of March Björn Einar Romören, a world cup jumper, did the first jump during a training session. This act started a significant chain of events. The biggest Norwegian web – magazines Verldens Gang and Aftenposten made this the head story and they invited the readers to interaction. Within 24 hours 11 000 comments were written, most of them in favor of Sagen and against Romören´s behavior. The Norwegian Ski Association excluded Romören from two World Cup competitions. What did happen during these days in the media?  I want to present the activities, which went on in two web-magazines, and analyze the articles written on the topic. Main issues are to show what an impact a social media network had on the sport in this specific case and how different actors appeared in the media and discuss if Romörens exclusion was a result of the mediatization.