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H Lode

Publications and source records attributed to H Lode.

At least 145 records · Page 8Linked to original sources

Multiple-dose pharmacokinetics of sparfloxacin and its influence on fecal flora.

In a randomized, double-blind, placebo-controlled, multiple-dose pharmacokinetic study, the safety and effect on intestinal flora of sparfloxacin (SPX) were determined in 12 healthy male volunteers (8 received SPX and 4 received a placebo). Following fasting and oral administration of 400 mg on day 1 and 200 mg on days 2 to 8, concentrations of the free drug in serum, urine, and feces were measured by high-performance liquid chromatography; serum and urine were also evaluated by a microbiological assay. All results, except those for renal excretion, exclude the glucuroconjugate metabolite. A mean peak concentration in serum (400-mg dose) of 0.56 +/- 0.13 mg/liter was measured 3.52 +/- 0.98 h after administration. Pharmacokinetic parameters (measured by high-performance liquid chromatography) were based on an open, one-compartment model and resulted in the following day 1 (calculated for the 200-mg dose), day 4 (recalculated for a single dose), and day 8 values (mean +/- standard deviation): area under the curve, 16.4 +/- 2.3 (day 1) and 18.3 +/- 5.1 (day 4) mg.h/liter; elimination half-life, 18.3 +/- 3.9 h; steady-state volume of distribution, 4.7 +/- 1.4 (day 1) and 4.3 +/- 1.2 (day 8) liters/kg; apparent total clearance, 201 +/- 31 (day 1) and 190 +/- 51 (day 4) ml/min; renal clearance, 19.1 +/- 5.8 (day 1) and 23.2 +/- 19.4 (day 4) ml/min. Recovery in urine on day 1 was 5.89% +/- 1.4% of the dose in 24 h for the parent compound and 18.4% +/- 6.8% for the SPX glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Simultaneous measurement of collagen type-VI-related antigen and procollagen type-III-N-propeptide levels in bronchoalveolar lavage.

Abnormal collagen metabolism is a hallmark of diffuse lung disease. Biochemical parameters which are correlated with collagen synthesis and degradation may be helpful to monitor fibrosis. In this study, we compared the sensitivity and specificity of procollagen type-III-N-propeptide (PIIINP) and collagen type-VI (C-VI) related antigen levels, as well as a ratio of both parameters (PIIINP/C-VI), in bronchoalveolar lavage fluid (BALF) from patients with diffuse and localized lung disease. We investigated 45 patients with diffuse lung disease (idiopathic pulmonary fibrosis (IPF), n = 21; sarcoidosis, n = 13; and lymphangitic carcinomatosis (LC), n = 11); 58 control subjects; and 92 patients with localized lung disease (bronchial carcinoma, n = 37; pulmonary tuberculosis, n = 31; and pneumonia, n = 24). C-VI and PIIINP were measured by immunoassay in concentrated BALF. Although the PIIINP and C-VI levels were increased in diffuse lung disease, the sensitivity of the individual parameters PIIINP and C-VI was low (IPF: PIIINP = 0.62, C-VI = 0.29; LC: PIIINP = 0.64, C-VI = 0.45; sarcoidosis: PIIINP = 0.69, C-VI = 0.15). When calculating the ratio of PIIINP/C-VI for each individual patient, we found a significant increase in this ratio in IPF (1.28 +/- 0.7), LC (2.34 +/- 1.2), and sarcoidosis (0.26 +/- 0.08) compared to both the controls (0.02 +/- 0.01) and other localized lung diseases (bronchial carcinoma 0.05 +/- 0.01; pulmonary tuberculosis 0.02 +/- 0.01), with the exception of pneumonia (0.18 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative pharmacokinetics of the new oral cephalosporins.

The comparative pharmacokinetics of the new oral cephalosporins (ester and nonester types), together with that of the first generation carbacephem, loracarbef, are considered in healthy volunteers. Also in this review, pharmacokinetic and microbiological data are combined in order to predict the possible clinical efficacy of this group of agents. Despite apparent similarities in the structure of these agents, single dose studies have revealed marked differences in the pharmacokinetics of the oral cephalosporins. Multiple dose studies showed no evidence of accumulation with these agents. In the elderly, only minor changes in the pharmacokinetics of the oral agents were observed, and were insufficient to warrant dosage adjustment. Unlike that of the nonester compounds, the bioavailability of the ester cephalosporins is increased when they are administered after food. Variable effects are observed when the ester agents are coadministered with antacids or H2-antagonists; while the absorption of cefetamet pivoxil was unaffected by coadministered antacids or H2-antagonists, the absorption of cefpodoxime proxetil was reduced.

Administration, Oral↗

Determination of a new cephalosporin, SCE-2787, in serum and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of a new-broad spectrum cephalosporin (I, SCE-2787) has been developed. The analyte was extracted from serum by precipitation of serum proteins with acetonitrile. Acetonitrile was extracted from the protein-free supernatant by dichloromethane. Urine was simply diluted with mobile phase. Separation was performed by ion-pair chromatography on a reversed-phase column (Nucleosil 5C18; 125 mm x 4.0 mm I.D.; 5 microns average particle size). The guard column was Perisorb RP18 (30 mm x 4.0 mm I.D.; 30-40 microns particle size). The mobile phase was acetonitrile-buffer solution containing 15 mM heptanesulphonic acid (pH 3.2) (4.5:95.5, v/v). Detection was performed at 235 nm with a diode-array detector, which also served to record ultraviolet spectra. The assay was sensitive, precise, accurate and fast. Specificity was controlled by on-line recording the ultraviolet spectrum of I and also by enzymic degradation with beta-lactamase. No interferences were observed during the analysis of serum and urine of healthy volunteers in pharmacokinetic studies.

Biological Assay↗

[A Q fever epidemic in Berlin. The epidemiological and clinical aspects].

An epidemic of Q fever in Berlin affected at least 80 patients (45 females, 35 males; age range 1-75 years). Sheep were identified as the focus of infection: they had been brought to a veterinary clinic because of nonspecific symptoms. The peak incidence of the infection was in April and May, 1992. Most of the patients were staff or students at the veterinary clinic. This is the most northern and, at the same time largest, Q fever epidemic recorded in Germany over the last 28 years. The complement fixation reaction (CFR) was not helpful diagnostically in the acute stage of the disease as it remained negative in the first 14 days (CFR < or = 1:5). Most of the patients had sudden fever to over 40 degrees C, severe headache and dry cough. Pulmonary infiltrates were seen in the chest radiograph of 8 of the 10 patients presented in this contribution. Auscultation was largely negative. Two patients had signs of hepatic involvement (GPT as high as 71 U/l). The drug of choice was doxycycline at a dosage of 200 mg twice daily for 14 days.

Adolescent↗

Pharmacokinetics of new oral cephalosporins, including a new carbacephem.

This review analyzes the pharmacokinetics of new oral cephalosporins, including esters, non-esters, and the carbacephem loracarbef, in healthy volunteers, as described in the literature and evaluated in several studies of our own. Single-dose studies have demonstrated considerable pharmacokinetic differences among these compounds. Cefixime, cefpodoxime proxetil, and cefetamet pivoxil are characterized by a low peak concentration and a prolonged half-life, while the other new agents have higher peak levels and shorter half-lives. Except for cefixime, the new oral cephalosporins are eliminated mainly by the kidneys. Pharmacokinetic studies in the elderly and in children indicate that the bioavailability of these agents is not influenced by age. Food increases the bioavailability of the ester cephalosporins but does not affect the absorption kinetics of the other new drugs.

Administration, Oral↗

Diagnostic problems in lower respiratory tract infections.

The main problems of diagnosis in lower respiratory tract infection are the differentiation of infection from colonization or contamination, and the isolation of a reliable and true pathogen. The clinical findings and differentiation of patients into those with pneumonia or infective exacerbations of chronic bronchitis should provide a definitive early diagnosis. Expectorated sputum may be unreliable in pneumonia, because of contamination by oropharyngeal flora. Although blood cultures may be negative, they provide a precise diagnosis and should be obtained in all pneumonias admitted to hospital. Other more invasive procedures are transtracheal needle aspiration, fibrebronchoscopic techniques including protected specimen brush and bronchoalveolar lavage with quantitative culturing and cytological analysis, transthoracic needle aspiration, thoracoscopy--guided biopsy and open lung biopsy. Any invasive procedure in a severely ill patient should be carefully directed weighing the risks as well as the benefits, whilst taking the underlying disease and expected survival into consideration.

Bacteria↗

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime.

Ceftazidime and the new SCE-2787 are parenteral cephalosporins with a broad antimicrobial spectrum. Pharmacokinetics, serum bactericidal activities, and side effects were investigated in a randomized crossover study. A total of 12 healthy volunteers received a 20-min infusion of 1.5 g of SCE-2787 or 2.0 g of ceftazidime. Serum and urine concentrations were determined by the bioassay method and by high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) drug concentrations in serum at the end of infusion of SCE-2787 and ceftazidime were 124.4 +/- 23.8 and 233.1 +/- 54.1 mg/liter, respectively. The urine recovery of SCE-2787 was 87.8% +/- 5.5% of dose in 24 h and for ceftazidime was 85.8% +/- 6.3% of dose in 24 h. Metabolites of SCE-2787 could not be detected by HPLC in serum or urine. Pharmacokinetic parameters were calculated both with a noncompartmental analysis and on the basis of an open two-compartment model (drugs are administered into and eliminated from a central compartment only. However, reversible drug distribution from the central space occurs simultaneously into one peripheral space). The area under the concentration time curve from 0 h to infinity of SCE-2787 was 197.9 +/- 25.4 mg.h/liter, and that of ceftazidime was 334.2 +/- 40.0 mg.h/liter. SCE-2787 had a mean terminal half-life in the elimination phase of 109.0 +/- 15.3 min, while that of ceftazidime was 99.0 +/- 13.4 min. The volume of distribution at steady state of SCE-2787 was 17.1 +/- 1.6 liters/70 kg, and that of ceftazidime was 122.9 +/- 1.3 liters/70 kg. The mean residence time of SCE-2787 was 136.4 +/- 15.4 min, and that of ceftazidime was 122.9 +/- 12.7 min. The renal clearance per. 1.73 m2 of SCE-2787 was 103.1 +/- 12.3 ml/min, and that of ceftazidime was 80.6 +/- 13.2 ml/min. The serum bactericidal activities were measured with the microdilution method of Stratton and Reller (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. One hour after administration, we measured mean reciprocal bactericidal titers of SCE-2787 and ceftazidime, respectively, against Escherichia coli of 388 and 243, against Klebsiella pneumoniae of 395 and 138, against Pseudomonas aeruginosa of 13.0 and 12.7, and against Staphylococcus aureus of 32.2 and 4.0. No severe side effects were observed in this single drug administration.

Adult↗