Beyond CL and V: A comprehensive approach to human pharmacokinetic predictions.

This article presents a comprehensive examination of processes related to the prediction of human pharmacokinetics (PK), a crucial task of clinical drug candidate selection. By systematically incorporating in vitro absorption, distribution, metabolism and excretion (ADME) and in vivo PK data with expert judgement, the study achieves high-quality human PK predictions for 40 orally administered compounds from Boehringer Ingelheim's new chemical entity (NCE) portfolio. Overall, the article provides a detailed evaluation of and guidance for a structured process to predict full concentration-time profiles beyond single-parameter predictions, using state-of-the-art methodologies.

Effects of CFTR-modulator triple therapy on sinunasal symptoms in children and adults with cystic fibrosis.

Purpose: Sinunasal symptoms and chronic rhinusinutitis are common in patients with cystic fibrosis. Cystic fibrosis transmembrane regulator (CFTR) modulators have led to dramatic improvements of respiratory symptoms and quality of life in patients with cystic fibrosis. This study aims to evaluate subjective and objective sinunasal symptoms after start of CFTR-modulator triple therapy.

Gene expression databases for physiologically based pharmacokinetic modeling of humans and animal species.

In drug research, developing a sound understanding of the key mechanistic drivers of pharmacokinetics (PK) for new molecular entities is essential for human PK and dose predictions. Here, characterizing the absorption, distribution, metabolism, and excretion (ADME) processes is crucial for a mechanistic understanding of the drug-target and drug-body interactions. Sufficient knowledge on ADME processes enables reliable interspecies and human PK estimations beyond allometric scaling.

Biodiversity, environmental drivers, and sustainability of the global deep-sea sponge microbiome.

In the deep ocean symbioses between microbes and invertebrates are emerging as key drivers of ecosystem health and services. We present a large-scale analysis of microbial diversity in deep-sea sponges (Porifera) from scales of sponge individuals to ocean basins, covering 52 locations, 1077 host individuals translating into 169 sponge species (including understudied glass sponges), and 469 reference samples, collected anew during 21 ship-based expeditions. We demonstrate the impacts of the sponge microbial abundance status, geographic distance, sponge phylogeny, and the physical-biogeochemical environment as drivers of microbiome composition, in descending order of relevance.