Gemfibrozil reporter

Lipid regulators gemfibrozil and bezafibrate frequently detected in wastewaters are reported to be eliminated in WWTPs with 46-69% [51] and 36-54% [13]. On the other side, clofibric acid was reported to be refractory pollutant for municipal WWTPs [22]. 

Fibrates are the most effective triglyceride-lowering agents and also raise HDL cholesterol levels. Combination therapy with a fibrate, particularly gemfibrozil, and a statin has been found to increase the risk for myopathy. Of the 31 rhabdomyolysis deaths reported with cerivastatin use, 12 involved concomitant gemfibrozil.25 Therefore, more frequent monitoring, thorough patient education, and consideration of factors that increase the risk as reviewed previously should be considered. 

Diphenhydramine, diltiazem, carbamazepine and norfluoxetine have been reported simultaneously in the same wild fish [107]. Moreover, diclofenac was found accumulating in vultures [119], fluoxetine, sertraline and the SSRl metabolites norfluoxetine and desmethylsertraUne were detected in fish [120]. Diclofenac bioaccumulation factors were 10-2,700 in the liver of fish and 5-1,000 in the kidney, depending on exposure concentrations [40, 121]. Gemfibrozil occurred in blood plasma of goldfish after exposure over 14 days at 113 times higher levels than in water [40]. 

Renal function //T pa/m enf. There have been reports of worsening renal insufficiency upon the addition of gemfibrozil therapy in individuals with baseline plasma creatinine greater than 2 mg/dL. In such patients, consider the use of alternative therapy against the risks and benefits of a lower dose of gemfibrozil. 

Lovastatin (Mevacor/ Altocor) [Antilipemic/HMG-CoA Reductase Inhibitor] Uses Hypercholesterolemia Action HMG-CoA reductase inhibitor Dose 20 mg/d PO w/ PM meal may T at 4-wk intervals to 80 mg/d max or 60 mg ER tab take w/ meals Caution [X, -] Avoid w/ grapefruit juice, gemfibrozil. Contra Active liver Dz Disp Tabs SE HA GI intolerance common promptly report any unexplained muscle pain, tenderness, or weakness (myopathy) Interactions T Effects W/ grapefruit juice T risk of severe myopathy W/ azole antifungals, cyclosporine, erythromycin, gemfibrozil, HMG-CoA inhibitors, niacin T effects OF warfarin >1 effects W/ isradipine, pectin EMS t Risk of photosensitivity Rxns T effects of warfarin concurrent EtOH use t risk of liver tox diltiazem and verapamil can T risk of lovastatin tox OD Unlikely to cause life-threatening Sxs... 

Figure 2.5 Reported concentrations of various PPCPs in Wastewater effluents by several research groups. On the x axis are respective PPCPs that are primarily cosmetics (1 = HHCB, 2 = AHTN, 3 = acetophenone, 4 = camphor, 5 = isobomeol, 6 = skatol, 7 = celestolide, i.e., AHMI, 8 = Phantolide, i.e., AHMI), the lotion ingredient (9 = methyl salicylate), two disinfectants (10 = triclosan and 11 = trilocarban), antihypertensive (12 = dehydronifedipine, 13 = diltiazem, 14 = bezafibrate, and 15 = gemfibrozil), analgesics and anti-inflammatories (16 = naproxen, 17 = ibuprofen, 18 = codeine), antimicrobials (19 = chlortetracycline, 20 = erythromycin, 21 = novobiocin, 22 = oxytetracycline, 23 = sulfamethaxazole, 24 = thiabendazole, 25 = trimethoprim), anxiolytic sedative (26 = carbamazepine), antidiabetic (27 = metaformin), reproductive (28 = 17(3 estradiol, 29 = 17a-ethinyl estradiol), GIT (30 = cimetidine, 31 = ranitidine), and respiratory (32 = Albuterol). The concentrations were compiled from Boyd et al. (2003), Gagne et al. (2006), Glassmeyer et al. (2005), Halden and Pauli (2005), Huang and Sedlak (2001), Ricking et al. (2003), and Temes et al. (2003).

Figure 2.11 Reported concentrations of various PPCPs in treated potable water by several research groups. So far reported are the analgesic (1 = naproxen), antihypertensive (2 = clofibric acid, 3 = dehydronifedipine, 4 = gemfibrozil), reproductive (5 = ethinyl estradiol, 6 = nor-ethindrone), antineoplasts (7 = metyhotrexate, 8 = bleomycin), sedatives (9 = carbamazepine, 10 = diazepam), and antimicrobials (11 = penicillin). Concentrations compiled from Boyd et al. (2003) and Collier (2007).

Nervous system adverse effects are rare, constituting 0.5% of all adverse effects (2). Gemfibrozil-induced headache has been reported (3) and occurred in one patient... 

Creatine kinase activity increased in five out of 1213 patients taking beclobrate (21). Myopathy during treatment has been reported with gemfibrozil (49) and ciprofi-brate (50,51). 

Gemfibrozil was suspected to have reduced libido in two cases (61,62), an effect that is well-known with clofi-brate, and four cases of loss of libido and impotence involving gemfibrozil have previously been reported (SEDA-13, 1325 63,64). 

Vasculitis, Raynaud s phenomenon, and polyarthritis have been reported with gemfibrozil (65). 

Rhabdomyolysis due to the combination of colchicine with gemfibrozil has been reported in a 40-year-old man with amyloidosis and chronic liver disease (70). 

In a retrospective series, 4 (5%) out of 80 subjects taking lovastatin and gemfibrozil developed a myopathy. Based on this and on reports to US Food and Drug Administration the combined use of the two drugs is discouraged, especially in patients with compromised renal and/or hepatic function. Elderly women may be at special risk (73,74). 

The last patient fared well on a combination of gemfibrozil and cerivastatin until he received influenza vaccination. Rhabdomyolysis has been reported with various... 

Ozdemir O, Boran M, Gokce V, Uzun Y, Kocak B, Korkmaz S. A case with severe rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy—a case report. Angiology 2000 51(8) 695-7. 

This finding depends on different factors and, as previously described, was partially solved by enhancing the turbulent flow on the membrane surface. In this way, the deposition of the substrate and the catalyst was limited, avoiding the concentration polarization phenomenon that also affects the water flux across the membrane. This aspect is currently under study and some preliminary results obtained in a study on the Gemfibrozil degradation in the described PMR are reported in Table 15.4. 

The British National Formulary (BNF) recommends that fibrates or nicotinic acid should not be combined with statins because of the potential for myopathy and rhabdomyolysis with this combination [54]. This is widely discussed in the medical literature. Numerous deaths have been reported and the high mortality associated with concurrent use of cerivastatin and gemfibrozil was partly instrumental in the decision to withdraw cerivastatin from the market in 2001 [34]. It appears that the high mortality in patients using concurrent gemfibrozil and cerivastatin was due to interactions at the level of glucuronidation, CYP2C8 inhibition and OATP inhibition [17, 55]. 

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