Search Results (3)

In temperate environments, climate change could affect water pH by inducing enhanced dissolution of CaSO₄ followed by biological sulphate reduction, with the potential to basify water due to H⁺ consumption. At the same time, increased atmospheric CO₂ could enhance weathering of carbonate rocks (e.g., dolomite) and increase the total concentration of dissolved carbonate species. Both processes enhance phototransformation by the carbonate radical (CO₃^•−), as shown for the non-steroidal anti-inflammatory drug paracetamol, provided that the dissolved organic carbon of water does not undergo important fluctuations. Climate change could also affect hydrology, and prolonged drought periods might considerably decrease flow rates in rivers. This is a substantial problem because wastewater pollutants become less diluted and, as a result, can exert more harmful effects due to increased concentrations. At the same time, in low-flow conditions, water is also shallower and its flow velocity is decreased. Photochemical reactions become faster because shallow water is efficiently illuminated by sunlight, and they also have more time to occur because water takes longer to cover the same river stretch. As a result, photodegradation of contaminants is enhanced, which offsets lower dilution but only at a sufficient distance from the wastewater outlet; this is because photoreactions need time (which translates into space for a flowing river) to attenuate pollution. Full article

Intravenous paracetamol is a commonly administered analgesic and antipyretic in inpatient settings. Paracetamol is metabolized by cytochrome P450 (CYP) enzymes followed by conjugating enzymes to mainly glucuronide but to a lesser extent, sulphate metabolites, and oxidative metabolites. Single nucleotide polymorphisms (SNPs) in the CYP enzymes result in modified enzymatic activity. The present study was carried out to evaluate the prevalence of SNPs related to paracetamol metabolism and principal metabolites in critically ill patients, and those with chronic kidney disease. The present study is a cross-sectional study carried out in adults (>21 years) requiring intravenous paracetamol as part of their standard of care. Details regarding their demographics, and renal and liver function tests were collected. Blood was withdrawn for the analysis of paracetamol and their metabolites, and the SNPs of key CYP enzymes. Paracetamol/paracetamol glucuronide (P/PG), paracetamol/paracetamol sulphate (P/PS) and PG/PS were estimated. Acute liver injury (ALI) and renal dysfunction were defined using standard definitions. We observed a significant prevalence of SNPs in CYP1A2*1C, CYP3A4*3, CYP1A2*1K, CYP1A2*6, CYP2D6*10, and CYP2E1*2 amongst the 150 study participants. Those with CYP1A2*6 (CC genotype) were observed with significantly lower PG and PS concentrations, and a higher P/PS ratio; CYP2D6*10 (1/1 genotype) with a significantly lower PG concentration and a higher P/PG ratio; and CYP1A2*1K (CC genotype) was observed with a significantly higher PG/PS ratio. Good predictive accuracies were observed for determining the SNPs with the cut-off concentration of 0.29 μM for PS in determining CYP1A2*1K, 0.39 μM for PG and 0.32 μM for PS in determining CYP1A2*6 genotype, and 0.29 μM for PG in determining the CYP2D6*10 genotype. Patients with renal dysfunction were observed with significantly greater concentrations of paracetamol, PG and P/PS, and PG/PS ratios, with a lower concentration of PS. No significant differences were observed in any of the metabolites or metabolite ratios in patients with ALI. We have elucidated the prevalence of key CYP enzymes involved in acetaminophen metabolism in our population. Alterations in the metabolite concentrations and metabolic ratios were observed with SNPs, and in patients with renal dysfunction. Population toxicokinetic studies elucidating the dose-response relationship are essential to understand the optimized dose in this sub-population. Full article

Given the great potential of porous carrier-based drug delivery for stabilising the amorphous form of drugs and enhancing dissolution profiles, this work is focussed on the synthesis and application of carbon onion or onion-like carbon (OLC) as a porous carrier for oral amorphous drug delivery, using paracetamol (PA) and ibuprofen (IBU) as model drugs. Annealing of nanodiamonds at 1100 °C produced OLC with a diamond core that exhibited low cytotoxicity on Caco-2 cells. Solution adsorption followed by centrifugation was used for drug loading and results indicated that the initial concentration of drug in the loading solution needs to be kept below 11.5% PA and 20.7% IBU to achieve complete amorphous loading. Also, no chemical interactions between the drug and OLC could be detected, indicating the safety of loading into OLC without changing the chemical nature of the drug. Drug release was complete in the presence of sodium dodecyl sulphate (SDS) and was faster compared to the pure crystalline drug, indicating the potential of OLC as an amorphous drug carrier. Full article