No abstract

Initial trough levels of ≥20 mg/L but not ≥15 mg/L were associated with early-onset VCM-associated nephrotoxicity in critically ill patients. Future prospective studies are needed to examine outcomes in critically ill patients achieving initial VCM trough levels of 15-20 mg/L.

No abstract

Some findings on the association between glaucoma and statins in the Asian population have been reported. We conducted a retrospective cohort study using health insurance claims data maintained by the JMDC Inc., which comprises data on about three million individuals representing 2.4% of the Japanese population. The association between the potency of statins and open-angle glaucoma in Japanese working-age population was examined using a commercially available health insurance claims and enrollment database. We identified 117,036 patients with a prescription of statins between January 1, 2005 and March 31, 2014; 59,535 patients were selected as new statin users. Of these, 49,671 (83%) patients without glaucoma who were prescribed statins for the first time were part of the primary analysis. New users of statin were defined as those with a prescription of statin at the beginning of the study, but without a prescription six months earlier. The cohort comprised 29,435 (59%) and 20,236 (41%) patients with a prescription of high-potency statin (atorvastatin and rosuvastatin) and low-potency statin (pravastatin, fluvastatin, pitavastatin, and simvastatin), respectively. Using Cox proportional hazards regression analysis, hazard ratios (HRs) were estimated for glaucoma adjusted for baseline characteristics. Although some baseline characteristics were not similar between the high-potency and low-potency statin groups, the standardized difference for all covariates was less than 0.1. No associations were found between high-potency statin use and glaucoma (adjusted HR = 1.08; 95% confidence interval, 0.93-1.24) in the primary analyses, using the risk for glaucoma in the low-potency statin group as reference. The risk of glaucoma with individual statin use was not significantly different from that with pravastatin. No significant association was found between high-potency statins and the increased risk of glaucoma in Japanese working-age population. Further studies are needed to examine the association between statins and glaucoma in the elderly population.

We investigated the characteristics of binding of tamsulosin to a a 1 -acid glycoprotein (AGP) genetic variants. The binding of tamsulosin to each of the human AGP variants was determined by ultrafiltration, and the binding characteristics for each variant were compared using binding parameters and inhibition of the binding by disopyramide and warfarin. The affinities of tamsulosin binding to a F1/S variant mixture and total AGP variants were relatively high (dissociation constants 1.6 m mM). On the other hand, the dissociation constant for variant A was 14.9؎2.53 m mM. The binding of tamsulosin was competitively inhibited by warfarin but not by disopyramide. Tamsulosin appears to be a suitable compound for studying the characteristics of drug binding to human AGP F1/S variants under clinical conditions.