Efflux and uptake transport and gut microbial reactivation of raloxifene glucuronides.

Raloxifene has low bioavailability due to extensive glucuronidation in the intestine and the liver, and its pharmacokinetics is associated with high intra- and interindividual variability. Some of this variability could be explained by the enterohepatic recycling of raloxifene, which is driven by transporter-mediated uptake and efflux and gut microbial deglucuronidation of raloxifene glucuronides. These individual processes involved in raloxifene disposition, however, have not been characterized in full detail.

Effects of fishing restrictions on the recovery of the endangered Saimaa ringed seal (Pusa hispida saimensis) population.

Over the past three decades, incidental bycatch has been the single most frequent verified cause of death of the endangered Saimaa ringed seal (Pusa hispida saimensis). Spatial and temporal fishing closures have been enforced to mitigate bycatch, which is mainly caused by the gillnets of recreational fishers. In this study, we employed an array of statistical machine learning methods to recognize patterns of death and to evaluate the impacts of annual fishing closures (15th April-30th June) on the recovery of the Saimaa ringed seal population during 1991-2021.

Does cytochrome 2D6 genotype affect the analgesic efficacy of codeine after ambulatory surgery? Prospective trial in 987 adults.

Background: Paracetamol-codeine combination tablet is widely used in pain management after day surgery. For safety reasons, its use has decreased in recent years. Codeine is a prodrug metabolised in the liver by the cytochrome P450 2D6 (CYP2D6) enzyme to morphine that produces the analgesic effect of codeine.

Candesartan Has No Clinically Meaningful Effect on the Plasma Concentrations of Cytochrome P450 2C8 Substrate Repaglinide in Humans.

In vitro evidence shows that the acyl--D-glucuronide metabolite of candesartan inhibits cytochrome P450 (CYP) 2C8 with an inhibition constant of 7.12 M. We investigated the effect of candesartan on the plasma concentrations and glucose-lowering effect of repaglinide, a sensitive clinical CYP2C8 index substrate.