PubMed Health⌕ Search

Biomedical subjects

K Borner

Publications and source records attributed to K Borner.

At least 73 records · Page 4Linked to original sources
PubMed1988

[Metronidazole-resistant trichomoniasis and successful therapy following high dosage].

A patient is reported who suffered for several months from a Trichomonas vaginalis infection that was resistant to the usual low-dose treatment with 5-nitro-imidazole derivatives. Following various ineffective therapeutic trials, the agent was isolated in order to determine its sensitivity to 5-nitro-imidazole. The resistance of the isolate to metronidazole was confirmed in vitro and in an animal experiment; the patient was therefore treated with high daily doses of metronidazole, 3 x 750 mg orally as well as 2 x 100 mg topically for 14 days. Substitution therapy with zinc was administered in order to normalize the patient's relatively low zinc serum levels. These measures finally led to a clinical cure and elimination of the pathogenic agent. This is the first confirmed case of a metronidazole-resistant Trichomonas vaginalis infection reported in the Federal Republic of Germany.

Adult↗
PubMed1987

Comparative efficacies of ciprofloxacin, ampicillin and chloramphenicol in treatment of experimental Haemophilus influenzae pneumonia.

An experimental murine model of bacteraemic Haemophilus influenzae pneumonia was used to evaluate the therapeutic efficacy of ciprofloxacin, as compared with ampicillin and chloramphenicol. An ampicillin-sensitive (AS) and an ampicillin-resistant (AR) challenge strain were employed. Ciprofloxacin treatment produced intrapulmonary killing of H. influenzae which was superior to that achieved with ampicillin (P less than 0.001, both strains) and chloramphenicol (P less than 0.001, strain AS; P less than 0.005, strain AR). Likewise, survival from strain AS pneumonia was 61% in the ciprofloxacin-treated animals, as compared with 43% for the chloramphenicol-treated, and 22% for the ampicillin-treated groups. We conclude that ciprofloxacin may be an effective agent in treating pneumonia caused by either ampicillin-sensitive or ampicillin-resistant strains of H. influenzae.

Ampicillin↗
PubMed1987

Therapeutic aminoglycoside monitoring in renal failure patients.

In patients with normal renal function, defined peak (5-10 mg/L) and trough levels (less than 2 mg/L) for gentamicin, tobramicin, and netilmicin are considered therapeutic. Netilmicin peak and trough levels were investigated in 50 patients requiring hemodialysis due to acute (70%) or permanent (30%) renal failure. Netilmicin was given at a dosage interval of 24 h, with a loading dose on the first day (1.5 mg/kg) and a reduced daily maintenance dose (0.5 mg/kg) supplemented to the posthemodialysis dosage (1.3 mg/kg) after each hemodialysis. As compared with studies on patients not requiring hemodialysis, mortality (44%) was higher, mainly due to uncontrolled infection, whereas ototoxicity (17%) was not. Peak (5.9 +/- 1.7 mg/L) and trough plasma levels (3.0 +/- 0.9 mg/L) were significantly lower in patients who did not respond and died than were peak (8.2 +/- 2.5 mg/L) and trough (3.8 +/- 1.2 mg/L) levels in patients responding to aminoglycoside treatment. In renal failure patients, there is obviously not only the risk of overdosing and toxic side effects but also the risk of insufficient bactericidal effect as a result of underdosing. Consequently, by use of an aminoglycoside dosage similar to the present schedule, peak levels (5-10 mg/L) as desired in normal subjects but trough levels (2.5-5 mg/L) that are considerably higher than in normal subjects should be the target concentrations for patients with advanced renal failure.

Acute Kidney Injury↗
PubMed1987

Prospective randomized controlled study of ciprofloxacin versus imipenem-cilastatin in severe clinical infections.

In a randomized prospective study, 66 patients with serious bacterial infections--mainly lower respiratory tract infections--were treated with either imipenem plus cilastatin (32 patients) or ciprofloxacin (34 patients); 30 patients in each group were evaluable for efficacy. Substantial underlying disease was present in most of the patients; pathogens isolated prior to treatment (77 isolates) consisted mainly of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and streptococci. Of the etiologic bacteria, 67% were eradicated by ciprofloxacin treatment and 79% by imipenem therapy; however, two patients (6.7%) failed in the ciprofloxacin group, and six patients (20%) did not respond to imipenem treatment (P = 0.25). All patients with therapeutic failures suffered from severe fatal underlying diseases, which had substantial impact on the outcome of treatment. Therapeutic drug monitoring in the ciprofloxacin patients revealed higher concentrations in serum at days 4 and 8 in comparison with day 1 of treatment, indicating that steady-state conditions were reached between days 1 and 4. The total number of side effects was relatively high--eight imipenem patients (25%) and six ciprofloxacin patients (18%) had reactions. Treatment had to be discontinued due to adverse reactions for three ciprofloxacin patients and two imipenem patients. Major side effects in both groups were gastrointestinal and central nervous system-related symptoms. In terms of clinical and bacteriological efficacy and safety, there was no statistical difference between the two groups, and both groups gave good to excellent results for bacterial infections that were difficult to treat.

Adolescent↗
PubMed1987

Comparative evaluation of enoxacin, ofloxacin, ampicillin, and chloramphenicol for treatment of experimental Haemophilus influenzae pneumonia.

A murine model of bacteremic Haemophilus influenzae type b pneumonia was used to evaluate the therapeutic efficacies of the quinolone antimicrobial agents enoxacin and ofloxacin compared with those of ampicillin and chloramphenicol. Ampicillin-susceptible (AS) and ampicillin-resistant (AR) challenge strains were employed. Treatment with enoxacin or ofloxacin produced intrapulmonary killing of H. influenzae that was superior to that achieved with ampicillin (P less than 0.01 to P less than 0.001 for both AS and AR strains). Ofloxacin and enoxacin also provided killing greater than that with chloramphenicol for the AS strain (P less than 0.01 to P less than 0.001). For the AR strain, ofloxacin provided killing greater than that obtained with chloramphenicol (P less than 0.001). Survival from AS strain pneumonia was 60% in enoxacin-treated and 78% in ofloxacin-treated animals compared with 41% for chloramphenicol-treated and 23% for ampicillin-treated groups. We conclude that enoxacin and ofloxacin may be effective antimicrobial agents in treating either AS or AR strains causing H. influenzae pneumonia.

Ampicillin↗
PubMed1987

Pharmacokinetics of ofloxacin after parenteral and oral administration.

In 10 volunteers, the pharmacokinetics of ofloxacin [HOE 280, DL 8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H -pyrido-[1,2,3-de] [1,4]benzoxacine-6-carboxylic acid] was determined after administration of 25, 50, 100, and 200 mg intravenously (30-min infusion) as well as 200 and 400 mg orally. Concentrations in serum and urine were measured by high-pressure liquid chromatography. Concentrations in serum following different parenteral ofloxacin dosages demonstrated dose dependency with long biological half-lives of 231 to 267 min. Pharmacokinetic parameters were calculated on the basis of open two- and three-compartment models, which yielded nearly identical results. High volumes of distribution (1.2 to 1.4 liters/kg of body weight) suggested effective diffusion into the extravascular space. High total and renal clearances indicated primarily renal excretion with additional elimination pathways, such as tubular secretion and extrarenal elimination. After oral administration, absorption was excellent, and the absolute bioavailability following 200 mg of ofloxacin could be calculated at greater than 0.95. Maximal concentrations in serum were attained 1.2 to 1.9 h after dosing; areas under the curve increased in proportion to dose between 200 and 400 mg of oral ofloxacin. The amount of known metabolites (demethyl and N-oxide compounds) excreted in urine reached only 4.3% (intravenously) and 4.0% (orally). Transient headaches in some volunteers were the only side effects registered.

Administration, Oral↗
PubMed1987

Comparative pharmacokinetics of new quinolones.

The pharmacokinetic properties of the new quinolones are characterised by a high volume of distribution, long biological half-life, low serum protein binding, elimination mainly by the kidneys, high total and renal clearances, limited biotransformation and a moderate to excellent bioavailability after oral administration. However, each quinolone derivative (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic characteristics, which should be considered in the treatment of patients, especially when liver and/or renal dysfunction exists.

Anti-Infective Agents↗
PubMed1987

Chrono-optimization of the time of evening administration with unequally divided twice-daily theophylline.

The effect of different times of evening administration (2000 hr versus 2200 hr) of sustained-release aminophylline (Euphyllin CR) on pharmacokinetics and lung functions was investigated in 30 patients presenting with moderately severe asthma. The study protocol followed a randomized three-period change-over design including a placebo period. As the dosing of the investigated SR-formulation is circadian rhythm adapted, the major part of the daily dose, namely 2/3, is affected by the change in time of administration. With regard to the nocturnal peak expiratory flow (PEF), no statistically significant difference between the times of evening administration was detected. However, the concomitant requirement for corticosteroids and inhaled beta-2-mimetics complicates the assessment of the relative clinical efficacy of the major dosing of theophylline during the 24 hr even though this drug is usually not given as a monotherapy in severe patients with reversible airway obstruction.

Adult↗
PubMed1986

[Biotransformation of selected gyrase inhibitors].

The common structure of the gyrase inhibitors norfloxacin, ciprofloxacin, pefloxacin, and ofloxacin is 3-carboxy-4-oxo-6-fluoro-7-(1-piperazinyl)-1,4-dihydro-quinolone. Several biotransformations of these substances are reported in the literature, mostly in animals and partly in humans: 1. Conjugation of the carboxylic acid to glucuronic acid (formation of an O-methyl ester of norfloxacin was found only in the rat); 2. Oxidation of the piperazine ring to the oxo derivative and subsequent metabolisation (or degradation) of the piperazine ring to several intermediates and finally to elimination of the side chain; 3. Substitution of the piperazine side chain to the 4-N-acetyl or 4-N-formyl-derivative (norfloxacin, ciprofloxacin); 4. Methylation of the 4-methyl-piperazine side chain (pefloxacin, ofloxacin). 5. N-oxidation of the 4-methyl-piperazine side chain (pefloxacin, ofloxacin). The glucuronides are microbiologically inactive. The activity of metabolites with a modified piperazine side chain varies from high (oxo derivatives) to low (after splitting of the ring). Quantitative data on the formation of the described transformation products in humans are presently still incomplete. The oxo derivative appears to be the main metabolite of norfloxacin and ciprofloxacin. Additional metabolites to the described ones are likely to be detected in the near future.

Anti-Infective Agents↗
PubMed1986

Pharmacokinetics of ciprofloxacin in healthy volunteers after oral and intravenous administration.

The pharmacokinetics of ciprofloxacin was studied in three groups of healthy volunteers comprising a total of 16 males and 16 females (age 21-35 years; body weight 52-80 kg). Single oral doses of 50, 100, 250, 500 and 750 mg were given to fasting subjects. The 250 mg dose was repeated after a breakfast. Intravenous doses of 50, 100 and 200 mg were given by short infusion in a randomized cross-over sequence. Concentrations of the drug in serum and urine were determined by high-performance liquid chromatography and by a microbiological assay. Mean peak concentrations between 0.37 +/- 0.49 mg/l (100 mg dose) and 1.97 +/- 0.50 (750 mg dose) were measured 60-75 min after oral administration. Twelve hours after 750 mg ciprofloxacin, serum concentrations were 0.15 +/- 0.05 mg/l. Taking a breakfast reduced absorption by 15-20% compared to the fasting state, as judged by peak concentrations, AUC and renal excretion. After 200 mg i.v. (20 min infusion period), initial serum concentrations of 4.0 +/- 1.2 mg/l were observed which declined 12 h later to 0.070 +/- 0.025 mg/l. Mean cumulated recovery of ciprofloxacin from urine over 24 h varied between 25.5% and 33.6% of oral doses and between 53.2% and 57.4% of intravenous doses. Two of the three metabolites seen in the chromatograms were identified as M1 and M3 (oxo-ciprofloxacin). Cumulated renal excretion after an oral 250 mg dose was 1.2 +/- 0.4% of M1 and 5.5 +/- 1.6% of M3.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Liquid chromatographic determination of ciprofloxacin and some metabolites in human body fluids.

Two column liquid chromatographic (HPLC) methods for the determination of ciprofloxacin and three metabolites are described. Both use reversed phase chromatography, the stationary phase being Nucleosil 5C18. Method A separates ciprofloxacin, metabolite M1 and another metabolite of unknown structure using fluorometric detection. Method B allows the determinations of metabolite M3 (oxo-ciprofloxacin) in urine by UV absorption. Serum was deproteinised with acetonitrile. Urine was diluted with buffer solution. The detection limit of ciprofloxacin was 0.010 mg/l serum and 0.2 mg/l urine and for the metabolite M3, 1 mg/l urine. Within-batch precision (coefficient of variation) for ciprofloxacin in serum was 0.8 to 2.4% and between-batch precision 4.8 to 9.3%. In urine within-batch precision was 1.7 to 2.1% and between-batch precision 2.4 to 7.2%. Recovery rates of ciprofloxacin from three groups of spiked sera was 94.5 +/- 2.6%, 97.2 +/- 1.1% and 95.0 +/- 1.8% and from urine 99.6%. Results obtained by HPLC (method A) were compared with those from a standard microbiological assay by means of bivariate regression analysis. In 12 subsets of data the slope of the regression line varied from 1.042 to 1.556. Significantly higher results from the microbiological assay were probably due to the presence of microbiologically active metabolites. We conclude that HPLC is the more specific method of determination. The described methods were applied for pharmacokinetic studies and therapeutic drug monitoring.

Biological Assay↗
PubMed1986

Ciprofloxacin: a comparative evaluation of its bactericidal activity in human serum against four enterobacterial species.

Serum bactericidal titres following a 200 mg i.v. dose of ciprofloxacin were measured in healthy volunteers and compared with those achieved with standard doses of ceftazidime, piperacillin and gentamicin, given alone or in combination. Five strains of each of four enterobacterial species were included in the study. Bactericidal titres 1 h after infusion of ciprofloxacin exceeded 1:16 for Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Enterobacter cloacae. While ceftazidime produced higher peak bactericidal titres against the Enterobacteriaceae, piperacillin was less effective than ciprofloxacin against three of the four enterobacterial species tested. Among the combinations, only piperacillin/gentamicin showed synergistic activity against some strains. Studies of bacterial killing kinetics again confirmed the high bactericidal activity of ciprofloxacin for the Enterobacteriaceae. The combination of ciprofloxacin with gentamicin resulted in more rapid killing of some strains of Klebsiella pneumoniae and Proteus vulgaris.

Adult↗
PubMed1985

[Current aspects of pseudomonas meningitis].

The article reports on the incidence, the conditions of occurrence, possibilities and successes of treatment with certain (combinations of) antibiotics, in dealing with cases of pseudomonas meningitis. The various possible substances used for treatment are discussed. Rates of penetration and CSF concentrations of azlocillin and cefsulodin are stated. Alternative possibilities for treatment are pointed out.

Aminoglycosides↗
PubMed1985

Pharmacokinetics of ciprofloxacin after oral and parenteral administration.

In 12 fasting volunteers, the pharmacokinetics of ciprofloxacin (Bay o 9867; 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carbonic acid) were determined after the administration of 50, 100, and 750 mg orally as well as 50 and 100 mg intravenously over 15 min. Serum and urine concentrations were detected with a bioassay. In addition, urine concentrations after a 50-mg dosing were measured by high-pressure liquid chromatography. The serum course of ciprofloxacin could best be described by an open three-compartment model. High volumes of distribution (exceeding 200 liters/100 kg) suggested effective diffusions in the extravascular space. The terminal half-life of ciprofloxacin ranged between 3 and 4 h. High total and renal clearances suggested additional elimination pathways, such as tubular secretion, metabolism, or biliary excretion. After oral administration, absorption was sufficient, and the absolute bioavailability varied between 0.77 and 0.63. Maximal serum concentrations were attained 0.5 to 1 h after dosing; the higher dosage tended towards a delay in absorption. The proportion of the relative amount of metabolites to the total amount of drug excreted in urine increased from 29.7% after intravenous administration to 42.7% after oral dosing, indicating a first-pass effect of the liver. Ciprofloxacin concentrations with a bioassay were 3 to 27% higher than with high-pressure liquid chromatography, which may indicate the presence of biologically active metabolites. No side effects were recorded.

Administration, Oral↗
PubMed1985

Comparative pharmacokinetics of ceftriaxone after subcutaneous and intravenous administration.

The pharmacokinetics of ceftriaxone (CRO) after subcutaneous and intravenous administration was studied in 10 healthy volunteers (5 males, 5 females, age 22-43 years, body weight 64.3 +/- 9.5 kg). Each of them received 2.0 g CRO i.v., and then 0.5 g i.v. and 0.5 g CRO s.c. in a randomized cross-over design. Subcutaneous administration of ceftriaxone was tolerable in combination with lidocaine. Serum and urine concentrations were determined by high performance liquid chromatography and for comparison with a bioassay. Mean serum concentrations were high after intravenous administration: 258 +/- 40 mg/1 (0 min, 2 g i.v.) resp. 84 +/- 40 mg/1 (0 min, 0.5 g i.v.). They declined to 11.6 +/- 4.2 mg/1 (2 g) resp. 6.5 +/- 2.2 mg/1 (0.5 g i.v.) within 24 h. Following subcutaneous application peak serum concentrations of 37.1 +/- 5.6 mg/1 were found after 138 +/- 49 min and a mean serum concentration of 6.6 +/- 1.6 mg/1 after 24 h. Concentrations of free ceftriaxone, determined by ultrafiltration, were 9.2 +/- 2.7% of total concentrations from 25 to 200 mg/1. Cumulated urine recoveries over a period of 24 h were: 51.2 +/- 8.9% (2 g i.v.), 47.1 +/- 7.9% (0.5 g i.v.) and 39.7 +/- 9.5% (0.5 g s.c.). There was no evidence for the presence of a microbiologically active metabolite in urine. Comparison of pharmacokinetic parameters for the 0.5 g dose did not show relevant differences between intravenous and subcutaneous administration (using an open two-compartment model): t beta 1/2 (min) 514 +/- 104 (s.c.), 592 +/- 133 (i.v.), VD,Area (1) 11.9 +/- 3.8 (s.c.), 13.3 +/- 3.8 (i.v.) and AUCtot (mg X h/1) 515 +/- 106 (s.c.) and 549 +/- 125 (i.v.). Bioavailability of the subcutaneous application was 0.96 +/- 0.26. For the 2 g i.v. dose the known nondosis-dependent kinetics was observed. Subcutaneous administration of ceftriaxone appears to be a possible alternative to the intravenous route in selected clinical situations or cases.

Adult↗