Pharmacokinetic-pharmacodynamic modeling of antipsychotic drugs in patients with schizophrenia Part I:The use of PANSS total score and clinical utility

<p>Background: To develop a pharmacokinetic-pharmacodynamic (PK-PD) model using individual-level data of Positive and Negative Syndrome Scale (PANSS) total score to characterize the antipsychotic drug effect taking into account the placebo effect and dropout rate. In addition, a clinical utility (CU) criterion that describes the usefulness of a drug therapy was calculated using the efficacy of the drug and dropout rates.</p><p>Methods: Data from 12 clinical trials in schizophrenia patients was used to quantify the effects of the antipsychotic drugs (APs), namely, haloperidol, risperidone, olanzapine, ziprasidone and paliperidone. Compartmental PK models were used to describe the time course of plasma drug concentrations. The combination of an E-max and the Weibull model was used to describe the drug and placebo effects. The steady-state drug concentrations were assumed to be the drivers of the exposure-response relationship. An exponential model was utilized to identify the predictors of probability of dropout. Simulations were performed to check the predictability of the model, and to calculate the CU of the drugs based on PANSS scores and dropout rates.</p><p>Results: The maximal drug effect (E-max) was highest for olanzapine whilst it was lowest for ziprasidone. Higher observed PANSS scores resulted in a greater likelihood of dropout. Taking into account the efficacy and the drop-out rate, all APs possessed a comparable CU at the therapeutic doses. The resulting PK-PD model parameters were used to compute the effective concentration and dose required to produce a clinically meaningful 30% drop in PANSS score from the baseline.</p><p>Conclusions: The developed PK-PD model and the associated CU score allow the evaluation of the time course of the PANSS scores of the different APs and a proper comparison of their clinically relevant treatments effects. (C) 2013 Elsevier B.V. All rights reserved.</p>

Intensify production, transform biomass to energy and novel goods and protect soils in Europe-A vision how to mobilize marginal lands

The rapid increase of the world population constantly demands more food production from agricultural soils. This causes conflicts, since at the same time strong interest arises on novel bio-based products from agriculture, and new perspectives for rural landscapes with their valuable ecosystem services. Agriculture is in transition to fulfill these demands. In many countries, conventional farming, influenced by post-war food requirements, has largely been transformed into integrated and sustainable farming. However, since it is estimated that agricultural production systems will have to produce food for a global population that might amount to 9.1 billion by 2050 and over 10 billion by the end of the century, we will require an even smarter use of the available land, including fallow and derelict sites. One of the biggest challenges is to reverse non-sustainable management and land degradation. Innovative technologies and principles have to be applied to characterize marginal lands, explore options for remediation and re-establish productivity. With view to the heterogeneity of agricultural lands, it is more than logical to apply specific crop management and production practices according to soil conditions. Cross-fertilizing with conservation agriculture, such a novel approach will provide (1) increased resource use efficiency by producing more with less (ensuring food security), (2) improved product quality, (3) ameliorated nutritional status in food and feed products, (4) increased sustainability, (5) product traceability and (6) minimized negative environmental impacts notably on biodiversity and ecological functions. A sustainable strategy for future agriculture should concentrate on production of food and fodder, before utilizing bulk fractions for emerging bio-based products and convert residual stage products to compost, biochar and bioenergy. The present position paper discusses recent developments to indicate how to unlock the potentials of marginal land