Publications

Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC).1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation.2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib.4-7.

Amorphous solid dispersions (ASDs) typically show improved dissolution and generate supersaturated solutions, enhancing the oral bioavailability of poorly soluble drugs. To gain insights into intraluminal ASD behavior, we utilized two poorly soluble drugs with different crystallization tendencies, atazanavir and posaconazole, prepared as ASDs at a 10% drug loading with hydroxypropyl methylcellulose acetyl succinate (HPMCAS). We evaluated their ...

Lipids in human intestinal fluids (HIF) form various structures, resulting in phase separation in the form of a lipid fraction and a micellar aqueous fraction. Currently used fed state simulated intestinal fluids (SIF) lack phase separation, highlighting the need for a deeper understanding of the effect of these fractions on intestinal drug solubilization in HIF to improve simulation accuracy. In this study, duodenal fluids aspirated from 21 ...

The organic cation transporter (OCT)-1 mediates hepatic uptake of cationic endogenous compounds and xenobiotics. To date, limited information exists on how Oct1/OCT1 functionally develops with age in rat and human livers and how this would affect the pharmacokinetics of OCT substrates in children or juvenile animals. The functional ontogeny of rOct/hOCT was profiled in suspended rat (2-57 days old) and human hepatocytes (pediatric liver tissue ...

Older adults are an inherently heterogeneous population with various underlying pathologies, medication use, and habits. In this study, the variability of this population was studied for the gastric and duodenal fluid volumes, as the amount of gastrointestinal volumes could play an essential role in the dissolution of drugs. The fluid volumes were retrospectively quantified by using magnetic resonance imaging (MRI). In 265 included fasted older ...

Paracetamol absorption kinetics show considerable variability in older adults, complicating the development of effective dosing regimens in the advanced-age population. In previous research, sparkling water has been shown to influence absorption-related processes. This study aimed to apply these findings to older adults and investigate the impact of sparkling water on absorption-related variability and early exposure. To this end, fourteen ...

To treat colonic diseases more effectively, improved therapies are urgently needed. In this respect, delivering drugs locally to the colon is a key strategy to achieve higher local drug concentrations while minimizing systemic side effects. Understanding the luminal environment is crucial to efficiently develop such targeted therapies and to predict drug disposition in the colon. In this clinical study, we collected colonic contents from an ...

Chikungunya virus (CHIKV) is a mosquito-borne virus transmitted by Aedes mosquitoes. While there are no antiviral therapies currently available to treat CHIKV infections, several licensed oral drugs have shown significant anti-CHIKV activity in cells and in mouse models. However, the efficacy in mosquitoes has not yet been assessed. Such cross-species antiviral activity could be favorable, since virus inhibition in the mosquito vector might ...

The development of pediatric oral drugs is hampered by a lack of predictive simulation tools. These tools, in turn, require data on the physiological variables that influence oral drug absorption, including the expression of drug transporter proteins (DTPs) and drug-metabolizing enzymes (DMEs) in the intestinal tract. The expression of hepatic DTPs and DMEs shows age-related changes, but there are few data on protein levels in the intestine of ...