Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents

Background: Pipamperone is a frequently prescribed antipsychotic in children and adolescents in the Netherlands, Belgium, and Germany. However, pediatric pharmacokinetics and the relationship with side effects and efficacy are unknown. Currently, divergent pediatric dosing recommendations exist. Objectives: The objective of this study was to describe the population pharmacokinetics of pipamperone in children and adolescents; to correlate measured and predicted pipamperone trough concentrations and predicted 24-h area under the curves with effectiveness, extrapyramidal symptoms, and sedation; and to propose dose recommendations based on simulations. Methods: Pipamperone concentrations were collected from Dutch pediatric patients in a prospective naturalistic trial (n = 8), and German pediatric patients in a therapeutic drug monitoring service (n = 22). A total of 70 pipamperone concentrations were used to develop a population pharmacokinetic model with non-linear mixed-effects modeling (NONMEM®). Additionally, an additional random sample of 21 German patients with 33 pipamperone concentrations from the same therapeutic drug monitoring service was used for external validation. Pharmacokinetic parameters were related to clinical improvement, sedation, and extrapyramidal symptoms. Simulations were performed to determine optimal dosages. Results: In a one-compartment model, the apparent volume of distribution was 416 L/70 kg and the apparent clearance was 22.1 L/h/70 kg. Allometric scaling was used to correct for differences in bodyweight. The model was successfully externally validated. The median [25th–75th percentile] measured pipamperone trough concentrations were numerically higher in responders (98.0 µg/L [56.0–180.5 µg/L]) than in non-responders (58.0 µg/L [14.9–105.5 µg/L]), although non-significant (p = 0.14). A twice-daily 0.6-mg/kg dosage was better than a fixed dosage to attain the concentration range observed in responders. Conclusions: Our findings suggest that pipamperone therapeutic reference ranges may be lower for children with behavioral problems than recommended for adults with psychotic symptoms (100–400 µg/L). When dosing pipamperone in children and adolescents, bodyweight should be taken into account

Statistics versus livelihoods: questioning Rwanda’s pathway out of poverty

Recent statistics indicate that poverty in Rwanda decreased impressively between 2006 and 2014. This seems to confirm Rwanda’s developmental progress. This article however argues for a more cautious interpretation of household survey data. The authors contrast macro-level statistical analysis with in-depth field research on livelihood conditions. Macro-economic numbers provide interesting information, however differentiated evidence is required to understand how poverty ‘works’ in everyday life. On the basis of the Rwandan case study, the authors conclude that because of the high political stakes of data collection and analysis, and given that relations of power influence the production of knowledge on poverty, cross-checking is crucial

BLOG - Les invisibles dans la production du savoir scientifique

“Bukavu series” cherche à offrir un espace pour ces voix qui sont souvent invisibles dans la production du savoir. Elle résulte d’un processus de réflexion collective et réflexive qui a commencé début 2018 et présente une série de blogs produits par un groupe de trente chercheurs basés à l’est de la RDC et en Europe. Pendant plus d’une année et demi, ces chercheurs ont examiné de façon critique leur propre position et (in)visibilité dans les cycles de recherche dans lesquels ils ont été impliqués. Ils ont exploré les défis éthiques et émotionnels auxquels ils sont confrontés pendant la recherche dans les milieux affectés par les conflits. De nombreux ateliers de réflexion ont offert un espace nécessaire pour partager l’expérience, réfléchir sur leurs rôles et place dans le processus de production du savoir ainsi que ce qu’il convient de faire pour le futur. Un processus collectif d’écriture a offert une opportunité supplémentaire aux chercheurs pour donner leurs points de vue sur la position et l’expérience des autres. Cette série de blogs met en exergue les résultats de ce processus