A proof of concept using the Ussing chamber methodology to study pediatric intestinal drug transport and age-dependent differences in absorption

Little is known about the impact of age on the processes governing human intestinal drug absorption. The Ussing chamber is a system to study drug transport across tissue barriers, but it has not been used to study drug absorption processes in children. This study aimed to explore the feasibility of the Ussing chamber methodology to assess...

Application of proteomics to understand maturation of drug metabolizing enzymes and transporters for the optimization of pediatric drug therapy

Drug disposition in children is different compared to adults. Growth and developmental change the processes involved in drug disposition and efficacy, including membrane transporters and drug metabolizing enzymes, but for many of these proteins, the exact changes have not been fully elucidated to date. Quantitative proteomics offers a solution...

Personal exposure assessment of pesticides in residents: the association between hand wipes and urinary biomarkers (Pre-proof)

Background: Residential exposure to pesticides may occur via inhalation of airborne pesticides, direct skin contacts with pesticide-contaminated surfaces, and consumption of food containing pesticide residues. The aim was to study the association of dermal exposure to pesticides between the use and non-use periods, between farmer and non-farmer...

Toxicokinetics of a urinary metabolite of tebuconazole following controlled oral and dermal administration in human volunteers

Tebuconazole (TEB) is a widely used triazole fungicide, but the toxicokinetics of its human metabolites are not fully described. For proper interpretation of biological monitoring data, knowledge on the metabolism and elimination of the compound is required. A human volunteer study was performed with the aim to describe the time courses of...

Corrigendum to ’Development of a mechanistic biokinetic model for hepatic bile acid handling to predict possible cholestatic effects of drugs’ [European Journal of Pharmaceutical Sciences 115 (2018) 175-184] (S0928098718300071) (10.1016/j.ejps.2018.01.007))

The authors regret the molar unit is incorrectly displayed on the x-axis in Fig. 4A and 4C and on the y-axis in Fig. 4B, 4D and Fig. 5. The correct versions of the figures are displayed below together with the unchanged legends. The authors would like to apologise for any inconvenience caused. DOI of original article: 10.1016/j.ejps.2018.01.007 ...

Development of a mechanistic biokinetic model for hepatic bile acid handling to predict possible cholestatic effects of drugs

Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic)...

Interaction of digitalis-like compounds with liver uptake transporters NTCP, OATP1B1, and OATP1B3

Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters...

Drug-drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of oatp1b1s

Organic anion-transporting polypeptide 1B1 (OATP1B1) is an important hepatic uptake transporter, of which the polymorphic variant OATP1B1*15 (Asn130Asp and Val174Ala) has been associated with decreased transport activity. Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with oral antidiabetics in the clinic. The aim of...

Interaction of immunosuppressive drugs with human organic anion transporter (OAT) 1 and OAT3, and multidrug resistance-associated protein (MRP) 2 and MRP4

Renal proximal tubule transporters can play a key role in excretion, pharmacokinetic interactions, and toxicity of immunosuppressant drugs. Basolateral organic anion transporters (OATs) and apical multidrug resistance-associated proteins (MRPs) contribute to the active tubular uptake and urinary efflux of these drugs, respectively. We studied...

P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful products of oxidative stress. We characterized...

Kinetics of plasma lysine after oral and parenteral administration to pigs