Inflammation can regulate hepatic drug metabolism enzymes and transporters. The impact of inflammation on renal drug transporters remains to be elucidated. We aimed to quantify the effect of inflammation (caused by acute pyelonephritis) on the in vivo activity of renal OAT1/3, using the probe drug furosemide. Pregnant women (2nd or 3rd trimester) received a single oral dose of furosemide 40 mg during acute pyelonephritis (Phase 1; n = 7) and after its resolution (Phase 2; n = 7; by treatment with intravenous cefuroxime 750 mg TID for 3-7 days), separated by 10 to 14 days. IL-6, IFN-γ, TNF-α, MCP-1, and C-reactive protein plasma concentrations were higher in Phase I vs Phase II. The pregnant women had a lower geometric mean [CV%] furosemide CLsecretion (3.9 [43.4] vs 6.7 [43.8] L/h) and formation clearance to the glucuronide (1.1 [85.9] vs 2.3 [64.1] L/h) in Phase 1 vs. Phase 2. Inflammation reduced the in vivo activity of renal OAT1/3 (mediating furosemide CLsecretion) and UGT1A9/1A1 (mediating the formation of furosemide glucuronide) by approximately 40% and 54%, respectively, presumably by elevating plasma cytokine concentrations. The dosing regimens of narrow therapeutic window OAT drug substrates may need to be adjusted during inflammatory conditions.

The significant environmental issue of water pollution caused by emerging contaminants un-derscores the imperative for developing novel cleanup methods that are efficient, economically viable, and that are intended to operate at high capacity and under continuous flows at the in-dustrial scale. This study shows the results of the operational design to build a prototype for the retention at lab scale of pollutants residues in water by using as adsorbent material, insoluble polymers prepared by β-cyclodextrin and epichlorohydrin as a cross-linking agent. Laboratory in batch tests were run to find out the adsorbent performances against furosemide and hydro-chlorothiazide as pollutants model. The initial evaluation concerning the dosage of adsorbent, pH levels, agitation, and the concentration of pharmaceutical pollutants enabled us to identify the optimal conditions for conducting the subsequent experiments. The adsorption kinetic and the mechanisms involved were evaluated revealing that that the experimental data perfectly fit the pseudo second order model being the adsorption process mainly governed by chemisorption. According to the KF constants values of 0.044 (L/g) and 0.029 (L/g) for furosemide and hydro-chlorothiazide, respectively and determination coefficient (R2) higher than 0.9 for both com-pounds, Freundlich yielded the most favorable outcomes, suggesting that the adsorption process occurs on heterogeneous surfaces involving both chemisorption and physisorption processes. The maximum monolayer adsorption capacity (qmax) obtained by Langmuir isotherm reveal a saturation of the β-CDs-EPI polymer surface 1.45 times higher for furosemide (qmax = 1.282 mg/g) than hydrochlorothiazide (qmax = 0.844 mg/g). Based on these results, the sizing design and building of a lab scale model were conducted, which in turn will be used later to evaluate its performances working in continuous flow in a real scenario.