[Study on the inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus].

OBJECTIVE: To discuss the inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus. METHODS: Used SDS-PAGE electrophoresis, spectrophotometry and semiautomatic biochemistry analysis to detect the accumulated concentration of norfloxacin, membranin electrophoretogram and the enzymatic activity in extracellular fluid before and after Coptis extract disposition. RESULTS: The accumulated concentration of medicine norfloxacin within the experiment strains which treated with Coptis extract was clear higher than that of the blank space (P < 0.01); some proteins which molecular weights were in 35 - 38 kDa rebound expressed after Coptis extract treated; The extracellular fluid enzymic activities of resistant Staphylococcus aureus had no significant difference (P > 0.05). CONCLUSION: The inhibit mechanism primarily of extracts from Coptis on clinical resistant the medicine of Staphylococcus aureus is the results of the combined action of various chemical composition and multi-target interaction, and the exact molecular mechanism remains to be further researched.

Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits.

Investigation was carried out in adult New Zealand white rabbits to study the influence of curcumin pre-treatment on pharmacokinetic disposition of norfloxacin following single oral administration. Sixteen rabbits were divided into two groups of eight each consisting of either sex. Animals in group-I were administered norfloxacin (100 mg/kg body weight p.o), while animals in group-II received similar dose of norfloxacin after pre-treatment with curcumin (60 mg/kg body weight per day, 3 days, p.o). Blood samples were drawn from the marginal ear vein into heparin-coated vials at 0 (zero time), 5, 10, 15, 30 min and 1, 2, 4, 6, 12 and 24 h post-treatment. Plasma norfloxacin concentrations were determined by high performance liquid chromatography. The plasma concentration-time profile of norfloxacin was adequately described by a one-compartment open model. The pharmacokinetic data revealed that curcumin-treated animals had significantly (p < or = 0.05) higher area under the plasma concentration time curve and area under the first moment of plasma drug concentration-time curve. Prior treatment of curcumin significantly (p < or = 0.05) increased elimination half-life and volume of distribution of norfloxacin. Further treatment with curcumin reduced loading and maintenance doses by 26% and 24% respectively.

Atención farmacéutica en antibioterapia: fluoroquinolonas / Antibiotherapy pharmaceutical care: fluoroquinolones

El incremento progresivo de microorganismos resistentes causantes de infecciones de difícil tratamiento ha llevado a la implantación de diversos programas destinados a evitar el abuso y mal uso de los antibióticos, al ser ésta una causa directamente relacionada con la aparición de resistencias. El objetivo de este estudio ha sido el de evaluar las pautas posológicas de las fluoroquinolonas prescritas en el ámbito comunitario en relación con su potencial eficacia, así como establecer un protocolo de actuación farmacéutica destinado a prevenir y evitar los PRMs más probables para este grupo de fármacos. Para ello se ha aplicado una metodología, previamente descrita, basada en la simulación de curvas de niveles de fármaco en sangre u orina considerando la variabilidad famacocinética asociada a las características demográficas de los pacientes. Los resultados obtenidos demuestran que las pautas de dosificación prescritas corresponden a unos estándares preestablecidos, independientemente de la edad o peso del paciente para el que se prescribe la quinolona. En consecuencia, las concentraciones de fármaco simuladas difieren significativamente de unos casos a otros, lo que puede no tener trascendencia clínica en infecciones urinarias debido a las altas concentraciones alcanzadas en orina, pero sí en infecciones de otro tipo, ya que los niveles en plasma simulados para ciprofloxacino son, en algunos casos, inferiores a los recomendados para optimizar la eficacia del tratamiento y minimizar la aparición de resistencias (AU)

Progressive resistance emergence responsible for infections with complicated treatments has lead to the establishment of different types of programs aimed at controlling the misuse of these drugs since the latter has been related to the emerging resistance. The aim of this study was to evaluate the dosage patterns of the fluoroquinolone prescriptions for the community patients in relation with its potential efficacy as well as to establish a protocol to be applied at the community pharmacy to avoid the most probable FRM for this group of drugs. The methodology used has been previously described and, briefly, it consists in the simulation of the urine and plasma drug levels taking into account the variability in pharmacokinetics, according to the demographics of the patient.The results show that a standard dosage pattern is prescribed with no consideration of the age and body weight, leading to a significant inter-variability in the simulated levels of the drug. This may not show clinical implications for urinary infections since these drugs concentrate in urine and reach sufficiently high values in this fluid. Nevertheless, despite urine levels simulated plasma concentrations of ciprafloxacin are in some cases lower than the recommended values for improving efficacy and reducing resistance emergence (AU)

Pharmaceutical properties of freeze-dried formulations of egg albumin, several drugs and olive oil.

The freeze-dried ternary formulations of meclizine (MZ, an anti-motion sickness drug), prednisolone (PRED, an anti-inflammatory drug) and norfloxacin (NFLX, an anti-microbial drug) which are poorly water-soluble and are low bioavailability drugs, were prepared using egg albumin and olive oil. The powder X-ray diffractions, the dissolution rate and the bioavailabilities in vivo of these formulations were studied in comparison with each drug alone. By forming ternary formulations of these drugs, the dissolution rates of the drugs from the formulations were significantly improved compared with each drug alone. The results of their powder X-ray diffraction measurements showed that these drugs in the ternary formulations presented in an amorphous form, indicating increased dissolution rates. On the other hand, the plasma concentrations of these drugs increased significantly after oral administration in formulations to rats, except for the NFLX formulation, and the areas under the concentration-time curves (AUC) of the ternary formulations of MZ, PRED and NFLX were 2.1, 1.6 and 1.3 times those of the drugs alone, respectively. From these results, it was proven that formulations consisting of egg albumin, olive oil and poorly water-soluble drugs were useful preparations for improving the drug's disadvantageous pharmaceutical properties.

Sequential mutations of gyrA in Escherichia coli associated with quinolone therapy.

A clinical isolate of Escherichia coli HM73 (MIC norfloxacin 2 mg/L) was isolated during norfloxacin therapy from an urinary tract infection in a patient who had been previously treated with pipemidic acid and infected by E. coli HM72 (norfloxacin 0.25), known to harbour a substitution Ser 83-->Leu in the gyrA gene. No difference in accumulation of norfloxacin was found between the two strains. DNA gyrases were isolated by affinity chromatography and assayed for supercoiling activity in the presence of norfloxacin. The minimal effective doses (MEDs) were 20 mg/L, for HM72 and 80 for HM73. DNA sequencing identified in HM73, two mutations leading to substitutions Ser 83 to Leu and Asp 87 to Gly.

Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration.

AIMS: This study was designed to assess the relative corneal penetration of topical drops of three antibiotics and to relate those levels to minimum inhibitory concentrations for organisms associated with bacterial keratitis. METHODS: Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.3% topical ophthalmic preparations) were given to 12 patients undergoing corneal transplantation. After the recipient tissue was removed, corneal drug penetration was measured using high performance liquid chromatography. RESULTS: Intracorneal concentrations of ofloxacin (geometric mean 0.81 mg kg-1) were significantly higher than both ciprofloxacin (0.60 mg kg-1; p = 0.048) and norfloxacin (0.54 mg kg-1; p = 0.012). Ciprofloxacin and norfloxacin concentrations did not differ significantly (p = 0.33). CONCLUSIONS: Review of the minimum inhibitory concentrations of the fluoroquinolones against ocular pathogens reveals that ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is in turn more potent than norfloxacin. These data favour the selection of ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment of corneal infection. The greater potency of ciprofloxacin offsets the superior penetration of ofloxacin. There is a need for improved clinical trial data concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some encouraging data are available for ciprofloxacin but not (in humans) for norfloxacin or ofloxacin.

Quinolone therapy in intensive care unit settings.

Three fluoroquinolone antimicrobials (norfloxacin, ciprofloxacin, and ofloxacin) could be used to prevent or treat infections in intensive care unit patients. All of these fluoroquinolones are particularly active against Gram-negative, aerobic bacteria. However, the pharmacokinetic properties of each fluoroquinolone are unique. Furthermore, only ciprofloxacin and ofloxacin are available for intravenous administration. Based on current, available information: a) fluoroquinolones are not endorsed for inclusion in selective decontamination protocols; b) fluoroquinolones are endorsed for empiric therapy of suspected Gram-negative bacterial infections based on local microorganism susceptibility patterns; and c) fluoroquinolones are endorsed for treatment of microbiologically documented infections based on their distribution properties, low rate of toxicity, and rapid bactericidal effect.

Ocular kinetics of pefloxacin after intramuscular administration in albino and pigmented rabbits.

We determined the ocular kinetics of pefloxacin, a new fluoroquinolone, when administered by the intramuscular route to albino and pigmented rabbits. In serum of albino rabbits, the area under the concentration-time curve (AUC) for the experimental period was 31.4 +/- 1.07 micrograms.h/ml (mean +/- standard deviation); the AUCs in the aqueous and vitreous humors were high (10.5 +/- 1.90 and 12.4 +/- 3.79 micrograms.h/ml, respectively). Pefloxacin was found in the avascular ocular tissues (30.15 +/- 3.79 micrograms.h/ml in the cornea and 6.98 +/- 1.06 micrograms.h/ml in the lens). In the vascularized tissues, the penetration ratio, defined as tissue AUC/serum AUC, was more than 1. The good intraocular diffusion of pefloxacin might be related to its low molecular weight and to its strong lipophilicity and could explain its clinical efficacy in the treatment of endophthalmitis. In pigmented rabbits, pefloxacin levels were high in the iris (1525 +/- 328 micrograms.h/ml, versus 40.2 +/- 5.08 micrograms.h/ml in albino rabbits) and chorioretina (2600 +/- 422 micrograms.h/ml, versus 48.3 +/- 7.52 micrograms.h/ml in albino rabbits), suggesting that it binds to the pigmentary apparatus.

Comparative in vitro activity of lomefloxacin, a new difluoroquinolone.

The in vitro activity of lomefloxacin, a new difluoroquinolone, was compared with that of norfloxacin, ciprofloxacin, gentamicin and ceftazidime against a total of 577 recent clinical isolates. MICs were determined by a standard agar dilution procedure, and two inocula (10(4) and 10(6) CFU) were used throughout. Lomefloxacin inhibited most species of the Enterobacteriaceae, Staphylococcus aureus (including methicillin-resistant strains) and Haemophilus influenzae at less than or equal to 1 mg/l. Pseudomonas aeruginosa (MIC 90, 4 mg/l) was somewhat more resistant, and Pseudomonas maltophilia (MIC 90, 16 mg/l) and the Bacteroides fragilis group (MIC 90, 32 mg/l) were considerably more resistant. Overall, lomefloxacin was as active as norfloxacin, but was two- to eightfold less active than ciprofloxacin against most species tested.

In vivo activity of ciprofloxacin, ofloxacin, norfloxacin and pipemidic acid against Escherichia coli infections in mice.

The therapeutic efficacy of four quinolones, i.e. ciprofloxacin, ofloxacin, norfloxacin and pipemidic acid, was investigated in experimental infections in mice caused by pipemidic acid-susceptible and -resistant E. coli. For intraperitoneal infections caused by E. coli strain 444 and 23, the efficacy of ciprofloxacin, ofloxacin and norfloxacin was superior to that of pipemidic acid. Furthermore, ciprofloxacin and ofloxacin had higher activity than norfloxacin and pipemidic acid in urinary tract and uterine infections. Serum and uterus levels of ciprofloxacin and ofloxacin in normal mice were higher and more durable than those of norfloxacin.

Resistance occurring after fluoroquinolone therapy of experimental Pseudomonas aeruginosa peritonitis.

Resistance emerging after fluoroquinolone therapy was investigated in a murine model of Pseudomonas aeruginosa infection. Mice were infected intraperitoneally by one of six strains and treated with pefloxacin or ciprofloxacin. In mice challenged with a low inoculum (1.6 X 10(5) CFU), no resistance occurred. With a higher inoculum (1.5 X 10(8) CFU) and after a single dose of antibiotic, posttherapy (PT1) strains with decreased susceptibility to quinolones (4- to 32-fold less) were isolated at a variable rate. The presence of talcum (125 mg) in the peritoneal cavity increased the risk of resistance after therapy. Pefloxacin (25 or 200 mg/kg) and ciprofloxacin (25 mg/kg) yielded similar resistance rates (61 to 77%), but ciprofloxacin (10 mg/kg) produced more resistance (83%) than did ciprofloxacin (50 mg/kg) (44%) (P less than 0.02). Combined with a quinolone, ceftazidime (P less than 0.001) or amikacin (P less than 0.01), but not piperacillin, reduced the emergence of resistance. After several doses of ciprofloxacin, it was found that 25-mg/kg doses every 12 h produced more resistance than did 25-mg/kg doses every 8 h or 50-mg/kg doses every 12 h. Compared with the preceding experiments using parent strains, ciprofloxacin and pefloxacin were less efficient in killing bacteria in mice infected with PT1 strains. Moreover, in one of these mice, a highly resistant PT2 strain (64-fold MIC increase for the quinolones) emerged. Besides increased MICs of the quinolones, there was a two- to eightfold increase in imipenem MIC for all PT1 and PT2 strains without alteration of other beta-lactam and aminoglycoside susceptibility. Some PT1 strains also showed a decreased susceptibility to trimethoprim and chloramphenicol. During therapy with a quinolone, resistance can emerge rapidly, especially when there is a large number of bacteria or a foreign body present. This risk may depend on the dosing schedule and may be reduced by combined therapy.

Ciprofloxacin and norfloxacin, two fluoroquinolone antimicrobials.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of ciprofloxacin and norfloxacin are reviewed, and mechanisms of antimicrobial resistance and drug and laboratory interactions are described. Norfloxacin is the first antimicrobial in the fluoroquinolone class to be marketed in the United States; ciprofloxacin is under investigation in clinical trials. The fluoroquinolones are structurally related to nalidixic acid. The activity and spectrum are enhanced by the addition of 6-fluoro and 7-piperazino substituents. Quinolone antimicrobials appear to inhibit DNA gyrase, an enzyme specific and essential for all bacteria, as their primary mechanism of action. As a result, DNA synthesis is inhibited. Ciprofloxacin and norfloxacin are active against gram-negative enteric bacteria, Pseudomonas aeruginosa, Haemophilus influenzae, and Neisseria gonorrhoeae. Ciprofloxacin has good activity against Staphylcoccus spp., including methicillin-resistant Staph. aureus. Norfloxacin generally is less potent than ciprofloxacin, particularly against Ps. aeruginosa and Staph. aureus. Peak concentrations occur about one to two hours after an oral administration of either drug. Both drugs are widely distributed in body fluids and tissues and are eliminated by renal excretion, metabolism, and biliary excretion. Dosage reductions are required in severe renal dysfunction. Ciprofloxacin and norfloxacin are effective agents for treating urinary-tract infections, including infections caused by Ps. aeruginosa. The recommended dosage of norfloxacin for urinary-tract infections in adults is 400 mg orally every 12 hours; the drug should be given for 7 to 10 days in uncomplicated infections and for 10 to 21 days in complicated ones. The fluoroquinolones may be useful for treating chronic bacterial prostatitis. Ciprofloxacin is potentially useful for treating sexually transmitted diseases. Ciprofloxacin is active against N. gonorrhoeae, including beta-lactamase-producing strains and strains that are resistant to tetracycline, and Chlamydia spp. Use of ciprofloxacin for treating gastrointestinal infections and for selective decontamination of the gastrointestinal tract is promising. In open studies, ciprofloxacin has been effective against a variety of infections caused by susceptible organisms. Resistance to ciprofloxacin has developed during treatment of infections caused by Ps. aeruginosa, Staph. aureus, and Serratia marcescens. The most frequently reported adverse effects of either drug are gastrointestinal complaints, headache, and dizziness.(ABSTRACT TRUNCATED AT 400 WORDS)

Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintenance treatment with theophylline.

Some of the new quinolone derivatives may be of value in the treatment of respiratory tract infections. It has been demonstrated that enoxacin, pefloxacin and ciprofloxacin, but not ofloxacin, decreased the metabolic clearance of the bronchodilator theophylline. This resulted in elevated plasma theophylline concentrations and, in some of the patients, theophylline toxicity. When the pharmacokinetic parameters of enoxacin, pefloxacin, ciprofloxacin and ofloxacin obtained in the present study were compared with those obtained from other studies in healthy volunteers not given concomitant theophylline, there was no evidence of theophylline influencing the clearance of the investigated quinolones.