Purpose Magnesium supplementation is an effective protective method against cisplatin-induced nephrotoxicity (CIN); however, there are few reports regarding the mechanism of its nephroprotective effect. The aim of this study was to determine whether premedication with intravenous magnesium prevents CIN and to determine the relationship between its nephroprotective effect and serum magnesium level. Methods Fifty-eight patients with head and neck cancer who received cisplatin, docetaxel, and 5-fluorouracil (DCF) were retrospectively investigated. Grade 2 or more serum creatinine elevation was defined as CIN. The incidence of CIN was compared between a magnesium sulfate (20 mEq, 2.46 g) premedication group and a non-magnesium group during the first cycle and in all cycles. Results CIN did not occur in any patients receiving magnesium premedication but did occur in 5 of 29 patients during the first cycle and in 6 patients during all subsequent cycles in patients who did not receive magnesium premedication. Furthermore, the variation of creatinine clearance was significantly worse in the non-magnesium group than in the magnesium premedication group from baseline. There was no difference in adverse effects or response rate between the two groups. Univariate analysis suggested that magnesium premedication significantly reduced the risk of CIN. On the other hand, serum magnesium depletion was seen in both groups to equal degrees despite supplementation. Conclusion Intravenous magnesium premedication has a protective effect on cisplatin-induced nephrotoxicity without the influence on the serum magnesium level. Magnesium premedication is a simple nephroprotective method that does not influence other adverse effects or rate of response to chemotherapy.
Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H receptor antagonists, are widely used among patients with cancer in clinical practice. The aim of the present study was to analyse the potential drug-drug interactions between MTX and gastric antisecretory drugs in high-dose MTX (HD-MTX) therapy. The impact of PPIs on the plasma MTX concentration on 73 cycles of HD-MTX therapy was analysed retrospectively in 43 patients. Also investigated was the involvement of OAT3 in PPI-MTX drug interaction in an in vitro study using human OAT3 expressing HEK293 cells. In a retrospective study, patients who received a PPI had significantly higher MTX levels at 48 h (0.38 vs. 0.15 μmol l , respectively, p = 0.000018) and 72 h (0.13 vs. 0.05 μmol l , respectively, p = 0.0002) compared with patients who did not receive a PPI (but received famotidine). Moreover, in vitro experiments demonstrated that PPIs (esomeprazole, lansoprazole, omeprazole and rabeprazole) inhibited hOAT3-mediated uptake of MTX in a concentration-dependent manner (IC values of 0.40-5.5 μ m), with a rank order of lansoprazole > esomeprazole > rabeprazole > omeprazole. In contrast to PPIs, famotidine showed little inhibitory effect on hOAT3-mediated MTX uptake. These results demonstrated that co-administration of PPI, but not famotidine, could result in a pharmacokinetic interaction that increases the plasma MTX levels, at least in part, via hOAT3 inhibition.
Doping is one of the most serious problems for athletes, and it is important that pharmacists have more interaction with athletes to ensure safer drug usage. Education is one of the most important roles of sports pharmacists, who are specialists regarding drug usage for athletes. We investigated pharmacy students' interests and comprehension regarding drug usage, doping and supplement intake by using the form of a questionnaire, since it is important to know how they understand these subjects as part of their greater educational program. The subjects were sophomore and junior pharmacy students at three universities. It was revealed that most of the students have negative images regarding doping violation, and they answered that they are familiar with doping. However, only sixteen percent of the students had attended lectures by specialists on doping. In addition, one third of pharmacy students did not know that some over-the-counter (OTC) drugs might contain doping substances. With regard to supplement intake, approximately two thirds of the respondents had an interest in and positive image of supplement intake. However, it was revealed that only one third of them recognized supplements as food, and their information regarding supplements was obtained from uncertain media. It was suggested that it is important for pharmacy students to have more opportunities to learn about what doping is. More education and enlightenment by sports pharmacists would be effective for pharmacy students as well as athletes, and it would help us to broaden the scope of what we can do for athletes and society.
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