Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, penicillinand quinolone-resistant Streptococcus pneumoniae, and vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus. The safety, tolerability, and pharmacokinetics of nemonoxacin were investigated in a double-blind, ascending-single-dose study involving 56 healthy subjects (48 males and 8 females) who were randomly assigned to 1 of 7 dose cohorts. In each successive cohort, two subjects received a placebo and six received single oral doses of 25, 50, 125, 250, 500, 1,000, or 1,500 mg nemonoxacin. Nemonoxacin was well tolerated up to the maximum dose of 1,500 mg. No severe or serious adverse events were observed. The most frequent adverse events were contact dermatitis, pruritus, and erythema. No clinically significant abnormalities were noted in the electrocardiograms, vital signs, or laboratory tests. The plasma concentrations increased over the dose range, and at 500 mg, the free area under the plasma concentration-time curve/MIC 90 ratios and free maximum nemonoxacin concentration/MIC 90 ratios against drug-sensitive/drug-resistant S. pneumoniae and S. aureus were greater than 227 and 24, respectively. The peak time and elimination half-life of nemonoxacin were 1 to 2 h and 9 to 16 h, respectively. The oral clearance was approximately 0.22 liter/h/kg. The plasma protein binding was approximately 16%. The results of this study support further evaluation of the multiple-dose safety, tolerability, and pharmacokinetics of nemonoxacin.Newer-generation quinolones are largely fluoroquinolones (FQs); they are characterized by the presence of a fluorine at the R6 position of the quinolone nucleus (2, 9, 19). Owing to their improved activity against Gram-positive and atypical pathogens, they have been widely used for the treatment and prophylaxis of bacterial infections. However, the use of FQs has been compromised by the emergence of bacterial resistance (3,8,14,18,22,30) and the potential for adverse side effects (15, 21), including ECG QTc interval prolongation, hepatotoxicity, and phototoxicity. Thus, there is an unmet need for newer compounds that are broad-spectrum agents effective against existing bacterial resistance and that have the potential to minimize the risk of use-limiting adverse effects.Nemonoxacin (TG-873870) (36), a novel nonfluorinated quinolone, has recently been developed from a series of 8-methoxy nonfluorinated quinolones (29) as a malate salt. It differs from FQs in that it lacks the fluorine at the R6 position (Fig. 1); this was formerly believed to be important for the antibacterial potency of FQs. Nemonoxacin has demonstrated broadspectrum activity (4, 20, 28) against Gram-positive, Gramnegative, and atypical pathogens. Furthermore, nemonoxacin appears to be more potent than several FQs, including ciprofloxacin, levofloxacin, and moxifloxacin (20). In preclinical studies, ...

Psyllium produces a modest but significant improvement in total cholesterol and LDL cholesterol levels in persons on either low-fat or high-fat diets. Psyllium, when added to a prescribed low-fat diet, may obviate the need for typical lipid-lowering medications or may prove to be a valuable adjunct to other treatments in patients with moderately elevated LDL cholesterol levels.

In response to the presence of certain compounds, rat liver weight can increase. Under the assumption that the liver density does not change, the liver volume will increase as well. To develop the capability to monitor this process noninvasively over time, we used liver volumes determined from MR images to estimate the in vivo liver volumes and weights of normal rats. We acquired multislice, spin-echo images from 18 rats using several protocols for suppression of motion artifacts. We found that volumes determined from data obtained using a combination of gradient moment nulling and respiratory gating, or a combination of signal averaging and "retarded" (after the pi pulse) phase-encoding, produced the most accurate estimates of in vivo liver volume and weight.

AimTo assess the influence of ketoconazole on azimilide pharmacokinetics. MethodsA two-period randomized crossover study was conducted in healthy male and female subjects (19-45 years). Placebo or 200 mg ketoconazole were administered orally every 24 h for 29 days. On day 8, a single oral dose of 125 mg azimilide dihydrochloride was coadministered following an overnight fast. Blood samples were obtained prior to and for 22 days following azimilide dihydrochloride administration. The plasma protein binding of azimilide was also assessed at 6 h after dosing. ResultsFollowing ketoconazole administration, a 16% increase in azimilide AUC (90% confidence interval (CI) 112%, 120%), a 12% increase in C max (95% CI 107%, 116%), a 13% increase in t 1/2,z (95% CI 107%, 120%) and a 14% decrease in CL o (95% CI 82%, 90%) were observed. ConclusionsThe changes in azimilide pharmacokinetics following ketoconazole treatment are not clinically important since the 90% CI for the AUC fell within the prespecified range of 80-125%. Thus, no clinically important drug interactions are expected when azimilide dihydrochloride is coadministered with CYP3A4 inhibitors.

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