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Biomedical subjects

H Lode

Publications and source records attributed to H Lode.

At least 253 records · Page 14Linked to original sources
PubMed1983

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

Eight healthy volunteers each received 2.0 g of ceftazidime by constant intravenous infusion over 20 min twice daily every 12 h for 8 days. Concentrations of ceftazidime in serum and urine were measured by a microbiological assay and by high-pressure liquid chromatography. Qualitative and quantitative studies on aerobic and anaerobic fecal flora were carried out before, during, and 2 weeks after the end of treatment. The mean (+/- standard deviation) maximum drug concentration in serum at the end of the 20-min infusion (day 1) was 185.5 +/- 28.5 micrograms/ml, decreasing to 0.8 +/- 0.4 microgram/ml after 12 h. The mean recovery of drug in urine at 12 h was 71.5 +/- 12.2%. Pharmacokinetic parameters calculated on the basis of a two-compartment model were as follows: elimination half-life, 110.5 +/- 15.2 min; volume of distribution at steady state, 21.2 +/- 2.6 liters/100 kg; volume of distribution by the area method, 26.2 +/- 4.0 liters/100 kg; area under the serum concentration-time curve, 293.3 +/- 47.8 micrograms X h/ml; total body clearance, 116.4 +/- 20.3 ml/min per 70 kg; renal clearance, 82.2 +/- 15.1 ml/min per 70 kg. The agar diffusion test and high-pressure liquid chromatographic analysis showed a good correlation of results. Metabolites of ceftazidime could not be detected by high-pressure liquid chromatography in serum or urine. No accumulation of ceftazidime could be observed during the 8-day study period. Mean maximum drug levels in serum were 185.5 to 214.5 micrograms/ml, and mean trough levels were 0.8 to 1.1 micrograms/ml (days 1 to 8). No severe side effects were noted. During ceftazidime treatment, anaerobes were left intact, whereas members of the family Enterobacteriaceae could be isolated from stool in only three of eight subjects. Two weeks after discontinuation of the drug, all stool specimens contained ampicillin- and cefazolin-resistant gram-negative rods.

Adult↗
PubMed1983

[Effect of doxycycline and isoconazole nitrate on human intestinal fungal flora].

29 patients from an outpatient department for pulmonary diseases were treated in randomized order with both doxycycline alone and in combination with 1-(2,4-dichloro-beta-(2,6-dichlorobenzyloxy)-phenethyl)-imidazole nitrate (isoconazole nitrate, Gyno-Travogen) 300 mg/day as well as 600 mg/day for 14 days. In 15 of the 29 patients, it was possible to detect Candida albicans in the stool before the beginning of therapy 10 patients being on a cortisone therapy with an average duration of 32.9 months. Under doxycycline monotherapy, a proliferation of the human intestinal flora by yeast-spp. did not occur. Furthermore, it was not possible to detect an effect of isoconazole nitrate on the human fecal intestinal flora.

Adult↗
PubMed1982

[Legionnaires' disease: prospective study of its incidence, clinical features and prognosis. (author's transl)].

In a prospective study (from April, 1980 to April, 1981) of 110 patients with moderately severe to severe pneumonia 11 were found to have 12 manifestations of Legionnaires' disease. Diagnosis was proven by indirect immunofluorescence tests, either a quadruple titre rise to 1 : 128 or a single titre of at least 1 : 256. The clinical picture in all 11 patients was the typical one of severe pneumonia, usually involving the lower lobes, high fever between 39 and 40.4 degrees C, as well as WBC counts between 6.8 and 28.9 X 10(9)/l. In nine cases artificial ventilation was required, in four there was acute renal failure requiring dialysis, in four other definite renal insufficiency. All patients had underlying disease, in some severe, such as chronic obstructive lung disease, diabetes mellitus, heart failure, liver cirrhosis, renal transplantation or extensive operations. Eight patients died, four of them of Legionnaires; disease. The relatively high infection rate (10%) indicates that in patients with risk factors, as well as those with a pneumonia unresponsive to the standard treatment within five to seven days, Legionnaires' disease should be considered in the differential diagnosis.

Acute Kidney Injury↗
PubMed1982

[Clinical picture of Legionnaires' disease (author's transl)].

Legionella infections can take the clinical course of a relatively harmless respiratory infection. However, serious, atypical pneumonia is a more frequent manifestation of infection with these pathogens. As yet, six different Legionella species can be identified; Legionella pneumophila appears to be the most common. Legionnaires' pneumonia is being found with increasing regularity during summer and autumn in elderly male patients with previous illnesses. The clinical picture is characterised by viral "prodrome", high fever, a dry cough, breast pain, confusion, diarrhoea, haematuria, moderate leukocytosis with lymphopenia, low concentrations of sodium in the serum and negative results from microbiological analysis of the sputum and pleural exudate. Diagnosis is confirmed culturally, microscopically and serologically; the indirect immunofluorescence test is of particular value for this purpose. Erythromycin alone or in combination with rifampicin is the treatment of choice.

Aged↗
PubMed1982

Pharmacokinetic studies of amoxicillin, potassium clavulanate and their combination.

Pharmacokinetic parameters after oral administration of 500 mg amoxicillin, 125 mg potassium clavulanate and 625 mg of their combination (augmentin) were determined in a randomized crossover study in ten healthy volunteers. The absolute bioavailability of amoxicillin (AUCoral/AUCi.v.) was 0.70 +/- 0.12. The mean maximum serum concentration of amoxicillin was 6.5 +/- 1.6 mg/l after administration alone and 6.5 +/- 1.4 mg/l after administration in combination. The respective values for potassium clavulanate were 3.4 +/- 1.4 mg/l and 2.8 +/- 1.1 mg/l. With both substances there was no significant difference between the pharmacokinetic parameters after administration alone and in combination. The AUC for amoxicillin was 19.5 +/- 5.4 h x mg/l after administration alone and 23.2 +/- 10.6 h x mg/l after administration in combination. The respective value for potassium clavulanate were 7.8 +/- 3.2 h x mg/l and 7.3 +/- 2.0 h x mg/l.

Administration, Oral↗
PubMed1982

Pharmacokinetics of cefadroxil and cefaclor during an eight-day dosage period.

The concentrations of cefadroxil and cefaclor in serum were studied in eight healthy volunteers receiving 1,000 mg of both substances three times per day for 8 days. Intraindividual comparisons showed an increase in peak serum levels of cefadroxil from days 1 to 8 in seven of eight volunteers. Cefaclor peak concentrations did not rise during the 8 days.

Adult↗
PubMed1982

Determination of apalcillin and its metabolites in human body fluids by high-pressure liquid chromatography.

We describe two methods for the quantitative analysis of apalcillin and its metabolites in serum and urine by reverse-phase high-pressure liquid chromatography (HPLC), a fast isocratic method for the parent drug, and a gradient method that allows the simultaneous assay of two metabolites. Serum was deproteinized with acetonitrile, and urine was diluted with buffer solution. The detection limit was about 0.5 micrograms/ml at a detection wavelength of 254 nm and 1.5 micrograms/ml at 310 nm. Within-batch precision (coefficient of variation) varied from 10.2 to 1.1% for concentrations of 7.8 and 185.3 micrograms/ml of serum, respectively. Recovery rates of 95.1 and 97.7% were found in spiked sera. Results obtained by HPLC correlated well with those from a standard microbiological assay (agar diffusion test); the resulting bivariate regression equation for serum was y-bioassay = 2.5 micrograms/ml + 0.992 X xHPLC, and that for urine was ybioassay = 12.0 micrograms/ml + 1.009 X xHPLC. At a detection wavelength of 315 nm, no interferences were observed in 10 healthy volunteers. Healthy subjects who were given 2 g of apalcillin intravenously excreted 18% of the parent drug within 24 h in the urine. Two inactive compounds were furthermore identified in urine as the isomeric forms of the penicilloic acids. Their excretion within 24 h amounted to 6.9 and 11.2% of the dose.

Ampicillin↗
PubMed1982

Supplementary dose after hemodialysis.

It is the aim of this paper to review in tabulated form the supplementary dose of drugs required after hemodialysis and to discuss the basic pharmacokinetics of these drugs in the presence of reduced renal function. This review is intended to point out practical aspects of clinical nephrology, It refers to data available from the literature. The descriptions of pharmacokinetics focus on the amount of drug in the body. The fraction of this amount removed by dialysis is replaced by the supplementary dose to maintain effective drug action. The rebound phenomenon affecting plasma drug levels after dialysis renders the calculation of the supplementary dose difficult. Linear extrapolation from plasma drug concentrations measured 6-12 h or more after dialysis may offer a solution to this problem.

Drug Administration Schedule↗
PubMed1982

Kinetic in vitro studies of antibacterial effects of the combination of new penicillins and cefalosporins against Proteus vulgaris.

In vitro studies simulating human as well as animal pharmacokinetics were performed in order to assess the combination effect of mezlocillin plus cefotaxime or cefoperazone. Different Proteus vulgaris strains exhibiting varying degrees of in vivo response to the antibiotics were selected for this study. Retardation of bactericidal efficacy was caused by the combination of mezlocillin plus cefoperazone in those strains exhibiting high degrees of beta-lactamase inducibility and being exposed to high levels of cefoperazone; lower drug levels caused indifferent effects. In any case, cultures were completely sterilized during the study period. Among the three beta-lactams studied, cefoperazone was the best beta-lactase inducer, while cefotaxime and mezlocillin exhibited only minor inducer activity. The combination of mezlocillin with cefotaxime, being only minimally active as beta-lactamase inducers, caused either indifferent or synergistic effects when simulating drug disposition in humans or animals. beta-Lactamase-negative strains exhibited only indifferent effects. The augmented bioavailability of mezlocillin due to its simultaneous administration with a cefalosporin resulted in an increased antibacterial efficacy.

Cephalosporins↗
PubMed1982

Pharmacokinetics and antibacterial efficacy in vivo of beta-lactam combinations against Proteus vulgaris.

The pharmacokinetics and antibacterial efficacy of mezlocillin, cefotaxime, cefoperazone and the mezlocillin/cefalosporin combinations, respectively, were studied by adopting the granuloma pouch model in rats. Exudate concentrations of mezlocillin were higher after combined i.v. injection with a cefalosporin as determined microbiologically and by high performance liquid chromatography (HPLC). Cefoperazone levels, however, were not affected. Not metabolized cefotaxime concentrations as determined by HPLC were also not increased following simultaneous injection with mezlocillin. Cefotaxime metabolite concentrations, however, were generally higher than unchanged cefotaxime and increased upon repeated administration of cefotaxime alone and to a greater extent when combined with mezlocillin. Antibacterial efficacy of mono- or combined chemotherapy was correlated to beta-lactamase inducibility of the test strains insofar as drugs acting as good or moderate enzyme inducers were ineffective in vivo. The combined therapy of mezlocillin with cefotaxime was effective in this case. This result was also correlated to the bioavailability of the beta-lactams in infected pouches. Due to the degree of beta-lactamase inducibility and production, drug levels were either decreased or not detectable.

Animals↗