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Norvir ritonavir ; Abbott Laboratories NYSE: ABT ; Norvir was approved by the FDA in March 1996 and is very rarely used as a protease inhibitor anymore. It is typically used as a boost for other protease inhibitors. Ritonavir is able to raise the blood levels of other drugs because it slows down the liver. The normal dose of ritonavir is 600 mg twice a day and the capsules, which are taken orally, are 100 mg a piece. Ritonavir should be taken with meals. When taken as a boost, ritonavir's dosing will change. Ritonavir can also be taken as a liquid. Ritonavir's side effects include nausea, vomiting, gas and diarrhea. It may also cause tingling or numbness around the mouth. These side effects caused approximately one third of patients to stop taking ritonavir. There is a generic version of ritonavir called Ritovir manufactured by Hetero Genix. Ritonavir appears to have a high anti-malarial effect making it very appealing to areas facing both HIV and Malaria epidemics.36 Fortovase Invirase saquinavir ; Roche Pharmaceuticals OTC: RHHBY.PK ; Invirase saquinavir in hard gel cap form ; , the first protease inhibitor, was approved by the FDA in December of 1995. Fortovase saquinavir in soft gel cap form ; , was approved by the FDA in November 1997. Because of its poor bioavailability, Invirase was phased out and the focus was shifted to Fortovase, the soft gel cap formulation. 1200 mg of Fortovase are taken 3 times a day. Each capsule is 200 mg so the patient will take six at a time. Fortovase should be taken with high-fat, high-protein food. Saquinavir is commonly boosted with ritonavir and a 1000 mg Invirase preferred when boosted with ritonavir ; dose combined with 100 mg ritonavir dose was approved by the FDA in 2003. The side effects of saquinvair are mild. They include nausea, diarrhea, upset stomach and heartburn. Saquinavir is currently being tested in a twice daily regimen.37 Reyataz atazanavir ; - Bristol-Myers Squibb NYSE: BMY ; Reyataz's active ingredient is atazanavir which was formerly known as BMS-232632. Reyataz was approved by the FDA in June 2003. Reyataz, unlike other protease inhibitors, does not lead to increases in blood fats. Physicians prescribe Reyataz for patients with high cholesterol, triglycerides, or any other risk factors for heart disease. A major benefit of atazanavir is that it can provide high enough blood levels to control HIV that may already be resistant to other protease inhibitors. Atazanavir is usually a 400 milligram capsule taken orally once a day. For patients who have taken protease inhibitors before, the dose may be reduced to 300 mg along with 100 mg booster of ritonavir Norvir ; . Patients must take multiple capsules when taking atazanavir because it comes in capsules of 100 mg, 150 mg and 200 mg. About 10% of the patients taking atazanavir are diagnosed with jaundice. Atazanavir may not increase the long-term risk of heart disease like other protease inhibitors because it does not increase the levels of fat or sugar in the blood. Side effects include possible changes in heart rhythm as well as common side effects associated with anti HIV drugs such as nausea, headache, rash, stomach pain, vomiting, diarrhea, tingling in hands or feet, and depression. Reyataz achieved sales of 4 million in 2004.38 Lexiva fosamprenavir ; GlaxoSmithKline NYSE: GSK ; Lexiva known as Telzir in Europe ; was approved by the FDA in October 2003. Fosamprenavir, the active ingredient in Lexiva, was formerly known as GW433908, or just 908. Fosamprenavir pro-drug ; is broken down in the patient's body to produce an active drug known as amprenavir. Fosamprenavir is not active against HIV; it becomes active against HIV when it becomes amprenavir. Fosamprenavir is promising because it might not be cross-resistant with other protease inhibitors. The normal dosage of Fosamprenavir is two 700 milligram tablets taken orally twice daily. Lexiva is also approved to be combined with ritonavir.

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1. Keating MJ, Chiorazzi N, Messmer B, et al. Biology and treatment of chronic lymphocytic leukemia. Hematology Soc Hematol Educ Program ; 2003; 153 75. Kipps TJ. Chronic lymphocytic leukemia. Curr Opin Hematol 1998; 5: 244 Schimmer AD, Munk-Pedersen I, Minden MD, Reed JC. Bcl-2 and apoptosis in chronic lymphocytic leukemia. Curr Treat Options Oncol 2003; 4: 211 Reed JC. Molecular biology of chronic lymphocytic leukemia. Semin Oncol 1998; 25: 11 Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 1993; 82: 1820 Adams J. The development of proteasome inhibitors as anticancer drugs. Cancer Cell 2004; 5: 417 Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999; 59: 2615 Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of In patients with severely obstructed vessels, myocardial flow depends on perfusion pressure, and a sharp decrease in BP may produce major ischemia and infarction. There is no evidence that phosphodiesterase-5 inhibitors improve the risk of acute myocardial infarction AMI ; , although enough evidence suggests a slight increase associated with sexual activity these drugs would indirectly raise the risk of events, because by allowing erection they expose men to sexual activity ; . Sildenafil is an oral phosphodiesterase inhibitor that enhances erectile function and was the precursor of its class. Sildenafil requires preserved libido and sexual stimulation to be effective, an association that results in nitric oxide release into the corpus cavernosum of the penis, stimulating guanylate cyclase and the subsequent formation of cyclic guanosine monophosphate, a substance that promotes smooth muscle relaxation in the arteries, arterioles, and sinusoids of the corpus cavernosum. This increases blood supply and causes.
Outside Curtain Area Three, Ross, now in green scrub shirt, sees DIANE LEEDS approaching. Inside Curtain Area Three, Dolores tries to maintain order amongst the scouts. Ross kisses Diane hello. Nice shirt. ROSS Occupational hazard. DIANE Any chance you can get off early? Jake and I are going house hunting. Inside, Goldman whips back a curtain. it with several scouts. Dr. Ross! She moves to the door. CONTINUED ; GOLDMAN She's been behind DIANE. Akemi, Inc. makes body-cooling vests, neck scarves, bandanas, seat cushions, foot wraps, mitts, and wrist bands designed to cool different parts of your body through evaporation. Each Body Cooler product is manufactured with special compartments containing non-toxic copolymer crystals. To activate the cooling, you soak the polymers in water for 20 minutes, pat the item dry with a towel, and apply to your skin for fast cooling relief. The crystals absorb up to 400 times their weight and keep cool for a day or two. Akemi may be contacted by calling 800 ; 209-2665, or through their website at bodycooler . Heat Relief DepotTM offers a wide variety of cooling products for individuals with MS. One of these is the MiraCoolTM fishing hat, a vintage-style reversible bucket hat to keep your head cool. MiraCool Cooling Crystals encased within the top of the 100-percent cotton fabric absorb and hold up to 1000 times their weight in cool refreshing water. The crystals work in combination with the evaporation process, so when worn against the head, cooling sensations are passed to pulse points and carried throughout the body. Just soak in cold water to activate and wear it wet or dry.

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Everal studies presented in Toronto provide further insight into the pathogenesis and treatment of metabolic problems in HIVinfected patients. Role of Specific Antiretrovirals The KLEAN study was a 46-week, randomized, open label study in which 878 antiretroviral-naive patients received either fosamprenavir ritonavir FPV r ; or lopinavir ritonavir LPV r ; , with a backbone of abacavir lamivudine in both arms [Eron J, et al. Abstract THLB0205; also Lancet 2006; 368: 476]. As reviewed elsewhere in this issue, antiviral efficacy was similar in both arms. Somewhat surprisingly, both arms were also similar in the effect on lipids. Fasting triglycerides TG ; increased by 59% in the FPV r arm and 66% in the LPV r arm at 48 weeks, while the use of lipid lowering medications was similar in both groups 11% ; . HDL also increased similarly in both arms 40% vs. 41% ; . The important message is that FPV r, which has been considered relatively "lipid friendly, " is also associated with significant increases in hypertriglyceridemia. One explanation for these findings is that the increases in TGs are the result of the boosting doses of ritonavir. The impact of low-dose ritonavir on lipids was addressed in a switch study that compared lipid changes in those switched to atazanavir ATV, n 559 ; or to ritonavir-boosted atazanavir ATV r, n 638 ; [Keiser P et al. Abstract WEPE0163]. While this , study was not randomized and therefore may be subject to confounding, a switch to ATV was associated with a 27% decrease in TGs, compared to a somewhat attenuated decrease of 20% in those who switched to ATV r. Another switch study quantified the lipid improvements in 88 patients who substituted ATV r for LPV r [Guillemi S, et al. Abstract WEPE0156]. After 6 months, there was an and fosrenol.
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Y. M. Ponce, M. A. C. Prez, V. R. Zaldivar, M. B. Sanz, D. S. Mota, and F. Torrens Internet Electronic Journal of Molecular Design 2005, 4, 124150 Table 5. Continued ; Prob Ha Prob MPb %Abs.d %Abs.e %Bio.f %Abs.g P%c 0.01 0.99 98.58 ; 0.72 0.28 43.63 ; 0.19 0.81 62.46 ; 0.00 1.00 100.00 5 poor 3 25 ; 0.00 1.00 99.96 1 ; 0.33 0.67 34.45 ; 64 3988 ; 0.00 1.00 99.32 1356 ; 0.03 0.97 94.91 ; 0.77 0.23 53.66 ~70 71 0.00 1.00 99.35 20100 ; 0.75 0.25 50.14 well 60A 3664 ; 59 4364 ; 0.83 0.17 66.16 ; 0.17 0.83 65.21 ; Drugs expected to have higher absorption 0.77 0.23 53.94 0.00 1.00 99.54 10 ; 0.19 0.81 61.16 ; 59 4968 ; 0.08 0.92 84.02 and fragmin!

Achieve a sensitive measurement of the vibratory sensation, we used a standardized method for vibration threshold determination 40, 41 ; . We found no improvement in the treated group compared with the placebo group, not even for participants with P-MMA 0.60 mol L. Nor did we find any associations between biochemical markers and other clinical manifestations after treatment. The symptoms and signs related to vitamin B12 deficiency are often vague and quite prevalent among the elderly. However, we did expect an improvement in symptom scores and signs among the treated participants compared with the placebo group. We found an improvement in neurologic symptoms in a subgroup but no improvement in the objective neurologic examinations, including measurement of the vibratory sensation. We therefore hesitate to put too much emphasize on this. The improvement in neurologic symptoms suggests that individuals with a P-MMA 0.60 mol L and neurologic symptoms may benefit from vitamin B12 treatment. In conclusion, our study confirms and expands earlier observations showing that treatment with vitamin B12 is efficient in reducing the metabolic markers P-MMA and P-tHcy. To decrease P-tHcy may be a goal in itself to reduce the risk of cardiovascular diseases. Because we observed only small improvements in clinical manifestations after treatment with vitamin B12, our results call into question whether decreasing mild to modestly increased P-MMA is clinically significant. Obviously, based on our results, we cannot judge whether prolonged treatment of patients with increased P-MMA will prevent the development of symptoms and signs of vitamin B12 deficiency. However, in light of those results, we agree with others 32, 42 ; expressing concern about widespread testing for mild vitamin B12 deficiency and about the use of a slight to moderate increase in P-MMA as the only indicator for treating people with vitamin B12.

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In millions of euros ; Subsidiaries more than 10% held French subsidiaries Laboratoires IREX S.A. N SIREN 380663914 22, Avenue Galile 92350 Le Plessis-Robinson Sanofi-Chimie ex.Sasy.1 ; S.A. N SIREN 428706204 9, rue du Prsident Allende 94250 Gentilly Sanofi-Synthlabo France ex. Sanofi Winthrop ; S.A. N SIREN 403335904 174, Avenue de France 75013 Paris Sanofi Winthrop Industrie S.A. N SIREN 775662257 82, Avenue Raspail 94250 Gentilly Secipe S.A. N SIREN 722019965 174, Avenue de France 75013 Paris Synthlabo Biomdical S.A. N SIREN 319740726 22, Avenue Galile 92350 Le Plessis Robinson Sanofi-Synthlabo Recherche S.A. N SIREN 713002269 1, Avenue P ossolette 91380 Chilly-Mazarin Sanofi-Synthlabo Groupe S.A. N SIREN 403335938 174, Avenue de France 75013 Paris Foreign subsidiaries Chinoin Pharmaceutical and Chemical Works Co Ltd Budapest, Hungary Sanofi-Synthlabo do Brasil Ltda Rio de Janeiro, Brazil Sanofi-Synthlabo Holding GmbH Berlin, Germany Sanofi-Synthlabo Inc New York, United States Sanofi-Synthlabo SA Barcelona, Spain Sanofi-Synthlabo SpA Milan, Italy Sanofi-Synthlabo UK Ltd Guildford, UK Sanofi-Synthlabo de Colombia S.A. Cali, Colombia Sanofi-Synthlabo Polholding BV Maassluis, Netherlands Sanofi-Synthlabo Produtos Farmaceuticos SA Alcabideche, Portugal Sanofi-Synthlao AE Peania, Greece Sanofi-Synthlabo AB Bromma, Sweden Sanofi-Synthlabo Kora Co. Ltd Seoul, South Korea 84 and frovatriptan. Multilocus sequence analysis approach demonstrated that under the generic name F. solani at least 45 phylogenetically distinct species exist, most of which have not been described formally. It is unknown if antifungal susceptibility varies among these phylogenetic species. If such differences exist, knowing them. 1 Engel TR, Laporte SM, Meister SG, et al: Tachycardia upon swallowing: Evidence for a left atrial automatic focus. J Electrocardiol 9: 69-73, 1976 Forsberg CW: Paroxysmal premature ventricular con tractions induced by swallowing: Case report. Lancet 53: 298-302, 1930 Kramer P, Harris L, Kaplan R, et al: Recurrent supraventricular paroxysmal tachycardia precipitated by swallow ing. Proc N EngI Cardiovasc Soc 21: 1962-63 Lindsay AE: Tachycardia Mechanisms and treatment. caused by swallowing: Heart J 85: 679-684 and fudr.

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14 R207910 + INH + PZA after one month of treatment but rendered lung cultures negative after 2 months. In the present study, the double drug combination R207910 + RIF reduced the bacillary load by one log10 less than the double drug combination R207910 + INH after one month of treatment, however this difference was not statistically significant. After 2 months of treatment the bacillary load was the same in these 2 groups. Thus a significant antagonism between R207910 and and fosamprenavir. A free weekly email update service brings news and information to users worldwide. Content includes national MS Societies' news, the latest research findings and people profiles highlighting individual experiences of living with MS. From early 2003, a free magazine `MS in Focus' will be available online in English, Spanish and German. The new World of MS website has been graphically and technically designed to simplify use for people disabled by MS. For further information contact: Chloe Neild, Information & Communications Manager, Multiple Sclerosis International Federation, Skyline House, 3rd Floor, 200 Union Street, London SE1 0LX. Tel. 0207 620 1911, Fax. 0207 620 1922, msif , E-Mail. chloe msif and fuzeon. MATERIALS AND METHODS A prospective, randomized, nonblinded, three-way crossover study of healthy adult HIV-negative volunteers was conducted to compare the PK parameters of FPV, APV, LPV, and RTV when FPV was administered simultaneously with, 4 hours prior to, or 12 hours prior to LPV RTV. Healthy volunteers were screened and enrolled if they were 18 to 45 years old, tested HIV seronegative by an enzyme-linked immunosorbent assay, and weighed 50 kg. Subjects were excluded if they had a previous hypersensitivity to APV, LPV, or RTV; were 20% over ideal body weight; were pregnant by positive serum human chorionic gonadotropin were taking concomitant prescription, nonprescription, herbal, or illicit drugs; were unable to abstain from alcohol or grapefruit products while enrolled; or had any of the following laboratory abnormalities: hematocrit of 30 g dl; total cholesterol level of 240 mg dl; triglyceride level of 400 mg dl; fasting glucose level of 120 mg dl; alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, or bilirubin level of more than twice the upper limit of normal; or albumin level of 3.5 g dl. The human experimentation guidelines of the U.S. Department of Health and Human Services and those of the University of North Carolina at Chapel Hill, as well as Health Insurance Portability and Accountability Act regulations, were followed in the conduct of this clinical research study. Subjects meeting the above criteria were initially given FPV and LPV RTV simultaneously for 10 days due to the potential drug-metabolizing enzyme-inducing capacities of APV 6, 27 ; and LPV RTV 30 ; . However, it was acknowledged that the lower drug exposures with this combination could potentially impact the maximal influence on drug-metabolizing enzyme activity. If the dose separation strategies successfully increased drug exposure, more time would be needed to achieve steady-state conditions. Therefore, after this initial phase, each subject in this prospective, nonblinded, three-treatment, three-period, sixsequence crossover study was assigned by a randomization schedule to one of the six treatment sequences described below ABC, ACB, BAC, BCA, CAB, and CBA ; , generated via SAS System software version 8.2 ; , as summarized in Table 1. The study design and randomization procedure specified a balanced allocation of 12 subjects to the six sequences, i.e., 2 subjects per sequence. On day 11, subjects began the assigned sequences with an initial treatment of either i ; FPV at 700 mg BID plus LPV RTV at 400 100 mg BID given simultaneously ; treatment A ; , ii ; FPV RTV at 700 100 mg BID plus LPV RTV at 400 100 mg BID given 4 h apart ; treatment B ; , or iii ; FPV RTV at 1, 400 200 mg once a day QD ; plus LPV RTV at 800 200 mg QD given 12 h apart ; treatment C ; . Each treatment was given for 7 days. On day 8, subjects were admitted to the General Clinical Research Center at UNC for intensive PK sampling. After the first PK visit, subjects crossed over to each of the other two treatments. Intensive PK sampling was performed at the end of each 7-day treatment. Fosamprenavir 700-mg tablets [investigational during the study period] [GlaxoSmithKline, Research Triangle Park, NC] ; , lopinavir ritonavir Kaletra; 133 33-mg capsules [Abbott Laboratories, Abbott Park, IL] ; , and ritonavir Norvir; 100-mg capsules [Abbott Laboratories, Abbott Park, IL] ; were supplied by GlaxoSmithKline and used throughout the study. The evening prior to PK sampling, study subjects were admitted to the Verne S. Caviness General Clinical Research Center at the University of North Carolina Hospitals. Evening doses of FPV, LPV RTV, and additional RTV if applicable ; were observed and recorded. Adherence was assessed by pill counts and medication administration records. After an overnight fast, the morning dose of each medication was administered with a standardized meal, and the time was recorded. For the visits in which the doses were separated, FPV RTV and LPV RTV were given with standardized meals. The total daily caloric intake per visit was standardized to 2, 000 to 2, 500 cal, made up of 55% carbohydrates, 30% fat, and 15% protein. Each PK sampling schedule varied in length depending on the treatment being investigated. For treatment A, blood samples were obtained at 0 h predose ; and 0.5, 1, 2, and 12 h after the doses of FPV plus LPV RTV. For treatment B, the blood sampling scheme was designed to characterize the full 12-hour PK.

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GlaxoSmithKline NYSE: GSK ; is one of the world's largest pharmaceutical companies, following the merger in 2001 of Glaxo Wellcome and SmithKline Beecham. It is the market leader in HIV therapies.81 GSK has four main therapeutic areas: anti-infectives, central nervous system, respiratory and gastrointestinal metabolic. The company also has a Consumer Healthcare portfolio comprising over-the-counter OTC ; medicines, oral care products and nutritional healthcare drinks. Its current medicines for HIV are amprenavir Agenerase ; , lamivudine + zidovudine Combivir ; , lamivudine Epivir ; , lamivudine + abacavir Epzicom ; , fosamprenavir Lexiva ; , zidovudine Retrovir ; , abacavir + lamivudine + zidovudine combination tablet Trizivir ; and abacavir Ziagen ; . GSK is also an industry leader in vaccine development. Research: Fixed-Dose Combinations GSK produces lamivudine + zidovudine Combivir ; , abacavir + lamivudine + zidovudine Trizivir ; and lamivudine + abacavir sulfate Epzicom ; . However, although GSK has a strong internal product line, it does not collaborate with outside companies to manufacture fixed-dose combinations. In July 2004, BI and GSK announced that they had "signed a letter of intent" to co-package BI's nevirapine and GSK's lamivudine + zidovudine.82 GSK informed us that "it was decided that the fastest way to get such a co-package to patients would be to work through one of our licensees, Aspen Pharmacare in South Africa." According to GSK, this co-package is already on the market in Africa and has been approved by the FDA.83 GSK has not stated plans to research a fixed-dose combination with BI. Rating: 2 Research: Neglected Diseases GSK has the most substantial neglected disease program in the industry. It has created a group within its R&D organization "to focus on diseases of the developing world." To date, GSK has thirteen clinical development programs targeting eight diseases particularly relevant to developing countries.84 It is the only pharmaceutical company with vaccines and drugs for malaria, tuberculosis and HIV in its pipeline. In June 2005, GSK announced plans to launch five vaccines over the next five years, for rotavirus, cervical cancer, pneumococcal disease, influenza and meningitis. It has brought Rotarix, for rotavirus, to market in several developing countries. Rotavirus is the leading cause of severe diarrhea in infants, killing 500, 000 children annually, mostly in developing countries and garlic.

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