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951.
Pharmacokinetics and safety of levofloxacin in patients with human immunodeficiency virus infection. 总被引:11,自引:3,他引:11 下载免费PDF全文
S D Goodwin H A Gallis A T Chow F A Wong S C Flor J A Bartlett 《Antimicrobial agents and chemotherapy》1994,38(4):799-804
Levofloxacin, the bacteriologically active isomer of ofloxacin, has microbiologic activity against many pathogens common in human immunodeficiency virus (HIV)-infected patients, including Mycoplasma species which may be cofactors in the progression of HIV disease. The purpose of this phase I, double-blind, randomized (1:1), placebo-controlled trial was to evaluate the pharmacokinetics and safety of levofloxacin hemihydrate in 10 asymptomatic HIV-infected males. Plasma concentrations by chiral high-performance liquid chromatography (HPLC) were evaluated for 48 h after a single 350-mg oral dose, at morning predose during the multiple-dosing phase, and for 72 h at steady state after a week of 350 mg every 8 h orally. Mean +/- standard deviation levofloxacin pharmacokinetic parameters (by noncompartmental moment method) after multiple dosing were as follows: area under the concentration-time curve, 31.24 +/- 5.60 mg.h/liter; apparent total body clearance, 11.18 +/- 1.76 liters/h; renal clearance, 8.63 +/- 2.82 liters/h; steady-state volume of distribution, 104.10 +/- 12.48 liters; and effective half-life, 6.50 +/- 0.51 h. Single-dose parameters were not significantly different from the multiple-dose parameters, with the exception of peak concentrations in plasma, which were 4.79 +/- 1.00 and 6.92 +/- 1.56 mg/liter for single- and multiple-dose data, respectively. Essentially identical parameter values were obtained from curve-fitting analysis when the entire 13-day plasma concentration profiles of the subjects were analyzed simultaneously by a two-compartmental distribution model. Levofloxacin pharmacokinetics in HIV-infected patients remained linear upon multiple dosing. The dosing regimen studied provides levels in plasma and urine well above those found to be effective in vitro against pathogens common in HIV-infected patients. Levofloxacin was well- tolerated in this group of asymptomatic HIV-infected males: there were no statistically significant differences in adverse effects in the two groups (P = 0.22). Use of placebo control helped to differentiate disease-related adverse effects from those related to the study drug. 相似文献
952.
Comparative In Vitro Activity of Newer Cephalosporins Against Anaerobic Bacteria 总被引:1,自引:5,他引:1 下载免费PDF全文
The in vitro susceptibilities of 408 recent clinical isolates of anaerobic bacteria against cefaclor, cephalexin, cephalothin, cefazolin, cefamandole, and cefoxitin were compared by an agar dilution technique. Against gram-positive bacteria, especially peptococci, peptostreptococci, and propionibacteria, cephalexin and cefaclor were significantly less active than cephalothin (P < 0.05). Cephalexin was also less active than cephalothin against clostridia and lactobacillus (P < 0.05). Against gram-negative bacteria, major differences were observed primarily with Bacteroides fragilis, against which cephalexin, cefazolin and cefoxitin were all significantly more active than cephalothin (P < 0.001). At concentrations of 16 μg per ml, however, all cephalosporins showed high in vitro activity, except against Lactobacillus species and B. fragilis. Cephalothin, cefazolin and cefamandole were considerably more active against the former, whereas cefoxitin was distinctly more active against the latter. 相似文献
953.
BACKGROUND: The cytochrome P450 CYP2D6 enzyme debrisoquine 4-hydroxylase metabolizes many different classes of commonly used drugs, such as tricyclic antidepressants and neuroleptics. Genetic polymorphism of the CYP2D6 gene is responsible for pronounced interindividual and interracial differences in the metabolism of these drugs. The CYP2D6*10 allele and its variants are the most frequent alleles found in Orientals, and they are responsible for diminished debrisoquine 4-hydroxylase activity because of the presence of a C(188)-->T mutation in exon 1. METHODS: One hundred nineteen Hong Kong Chinese subjects were genotyped by means of allele-specific PCR, PCR, and restriction enzyme analysis for 10 CYP2D6 alleles (CYP2D6*1, *2, *4D, *5, *8/*14, *10A, *10B, *15, *16, and J9). RESULTS: CYP2D6*10B was the most prevalent allele, and CYP2D6*10/CYP2D6*10 was the most frequent genotype, representing 41.17% [corrected] of the population. CONCLUSIONS: There was no significant difference in the prevalence of the alleles analyzed between our study and the Chinese populations genotyped previously. This is the largest study in terms of the number of CYP2D6 alleles analyzed in an Oriental population and the first one conducted in a Hong Kong Chinese population. 相似文献
954.
Mutations in the aph(2")-Ic gene are responsible for increased levels of aminoglycoside resistance 下载免费PDF全文
Lee HK Vakulenko SB Clewell DB Lerner SA Chow JW 《Antimicrobial agents and chemotherapy》2002,46(10):3253-3256
Random PCR mutagenesis of the enterococcal aph(2")-Ic gene followed by selection for mutant enzymes that confer enhanced levels of aminoglycoside resistance resulted in mutants of APH(2")-Ic with His-258-Leu and Phe-108-Leu substitutions, all of which conferred rises in the MICs of several aminoglycosides. The mutated residues are located outside conserved regions of aminoglycoside phosphotransferases. 相似文献
955.
956.
Absence of age and gender effects on the pharmacokinetics of a single 500-milligram oral dose of levofloxacin in healthy subjects. 总被引:2,自引:4,他引:2 下载免费PDF全文
S C Chien A T Chow J Natarajan R R Williams F A Wong M C Rogge R K Nayak 《Antimicrobial agents and chemotherapy》1997,41(7):1562-1565
The influence of age and gender on the pharmacokinetics of levofloxacin in healthy subjects receiving a single oral 500-mg dose of levofloxacin was investigated in this parallel design study. Six young males (aged 18 to 40 years), six elderly males (aged > or = 65 years), six young females (aged 18 to 40 years), and six elderly females (aged > or = 65 years) were enrolled and completed the study. The study reveals that the bioavailability (rate and extent) of levofloxacin was not affected by either age or gender. In both age (young and elderly) and gender (male and female) groups of subjects, peak concentrations in plasma were reached at approximately 1.5 h after dosing; renal clearance of levofloxacin accounted for approximately 77% of total body clearance, and approximately 76% of the administered dose was recovered unchanged in urine over the 36 h of collection. The apparent differences in the calculated pharmacokinetic parameters for levofloxacin between the age groups (young versus elderly) and between the gender groups (males versus females) could be explained by differences in renal function among the subjects. A single dose of 500 mg of levofloxacin administered orally to both young and old, male and female healthy subjects was found to be safe and well tolerated. As the differences in levofloxacin kinetics between the young and the elderly or the males and the females are limited and are mainly related to the renal function of the subjects, dose adjustment based on age or gender alone is not necessary. 相似文献
957.
Comparative in vitro activity of ceftizoxime, cefoperazone, and cefoxitin against anaerobic bacteria 总被引:2,自引:6,他引:2 下载免费PDF全文
Against 482 obligate anaerobes studied by the agar dilution technique, ceftizoxime was significantly more active than both cefoxitin and cefoperazone (P less than 0.001); the latter two agents were comparable in activity. The enhanced activity of ceftizoxime, as compared with the activity of cefoxitin, was against both gram-positive and gram-negative anaerobes (especially Lactobacillus and bacteroides spp). Cefoperazone, however, was more active than cefoxitin against gram-positive anaerobes (particularly Lactobacillus spp.) but was less active than cefoxitin against gram-negative anaerobes (particularly Bacteroides fragilis and Veillonella spp.). 相似文献
958.
J J Albers G R Warnick D Wiebe P King P Steiner L Smith C Breckenridge A Chow K Kuba S Weidman H Arnett P Wood A Shlagenhaft 《Clinical chemistry》1978,24(6):853-856
Plasma high-density lipoprotein is commonly estimated by measuring the cholesterol remaining in plasma supernatant solutions after other lipoproteins, which contain apolipoprotein B, are precipitated with heparin and Mn2+. The method (method I) now in use by the Lipid Research Clinics, in which Mn2+ is at 46 mmol/liter final concentration, is reasonably accurate, but precipitation and sedimentation of lipoproteins other than high-density lipoproteins is often incomplete. We evaluated two modifications of method I. In method II, the Mn2+ concentration was doubled; the second modification (method III) included the increased Mn2+ concentration in a combined heparin Mn2+ reagent, decreased sample volume (2 ml), and a shorter incubation time (10 min at room temperature). The percentages of samples with turbid supernates (i.e., incomplete sedimentation) by methods I, II, and III were 9, 3, and 2%, respectively. Among non-turbid supernates, the percentages of samples containing measurable apolipoprotein B (incomplete precipitation) were 79, 19, and 16%, respectively. We conclude that method III is the most convenient and accurate of the three procedures. 相似文献
959.
Comparative Susceptibility of Anaerobic Bacteria to Ticarcillin, Cefoxitin, Metronidazole, and Related Antimicrobial Agents 总被引:1,自引:5,他引:1 下载免费PDF全文
David K. Henderson Anthony W. Chow Lucien B. Guze 《Antimicrobial agents and chemotherapy》1977,11(4):679-682
The in vitro antimicrobial activity of two newer agents, ticarcillin and cefoxitin, against 204 recent clinical isolates of anaerobic bacteria was determined by an agar dilution technique, and compared to their related compounds carbenicillin, cephalothin, and penicillin, as well as metronidazole, clindamycin, and chloramphenicol. Ticarcillin was similar to carbenicillin, and cefoxitin was more active than cephalothin. At readily achievable blood concentrations of each antimicrobial agent, ticarcillin was slightly less active than clindamycin against Bacteroides fragilis. Cefoxitin was superior to cephalothin and penicillin against B. fragilis. Penicillin remained highly active against all obligate anaerobes other than B. fragilis. Metronidazole, while highly effective against B. fragilis and Clostridium perfringens, was only intermediately effective against anaerobic gram-positive cocci and relatively inactive against nonsporulating anaerobic gram-positive bacilli. Further evaluation of the clinical efficacy of ticarcillin, carbenicillin, and cefoxitin against anaerobic infections is indicated. 相似文献
960.
Howard P. Glauert Mark M. Beaty Terry D. Clark Wendy S. Greenwell Vickie Tatum Li -Chuan Chen Tim Borges Terri L. Clark Suseela R. Srinivasan Ching K. Chow 《Journal of cancer research and clinical oncology》1990,116(4):351-356
Summary The purpose of this study was to determine the effect of the dietary antioxidant vitamin E on hepatocarcinogenesis by peroxisome proliferators which, it is hypothesized, induce tumors by increased production of hydrogen peroxide or other oxygen radicals. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (10, 50, or 500 ppm) of-tocopheryl acetate for 6 months or 21 months. The incidence of hepatic tumors and the number and volume of-glutamyl-transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci were quantified. No tumors or altered hepatic foci were seen at 6 months, but at 21 months the incidence of hepatic tumors and the number and volume of altered hepatic foci were increased in rats fed higher levels of vitamin E. Indices of oxidative damage — concentrations of malonaldehyde, conjugated dienes, and lipidsoluble fluorescence products — were not affected or were lower in rats fed higher amounts of vitamin E; the enhancing effect of vitamin E on the development of altered hepatic foci and hepatic tumors, therefore, was not related to the induction of cellular oxidative damage. Hepatic peroxisomal fatty acid-oxidation and vitamin C concentrations were not affected by vitamin E, whereas the glutathione concentration was decreased in rats fed higher amounts of vitamin E. This study shows that increasing the vitamin E content of the diet enhances ciprofibrate-induced hepatocarcinogenesis, but the mechanism of this effect is unclear.Abbreviations GGT
-glutamyl transpeptidase
- G6Pase
glucose-6-phosphatase
Supported by American Institute for Cancer Research grant 86B66 and National Cancer Institute grant CA43719. 相似文献