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G Höffken

Publications and source records attributed to G Höffken.

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

The pharmacokinetics of ticarcillin, clavulanic acid and their combination.

The pharmacokinetics of ticarcillin and clavulanic acid were examined both alone and combined (3.0 and 5.0 g ticarcillin + 0.2 g clavulanic acid as 3.2 or 5.2 g Timentin) after a 15-min infusion in ten healthy volunteers. The serum kinetics of both ticarcillin and clavulanic acid were described by an open two-compartment model. After the end of the infusion, the serum concentrations of ticarcillin (clavulanic acid) ranged between 576.2 +/- 98.7 mg/l (26.1 +/- 2.6 mg/l) after separate and 621.8 +/- 62.6 mg/l (22.9 +/- 4.6 mg/l) after combined administration. Both substances showed similar kinetic behaviour in serum with a T1/2 beta of 74.8 +/- 11.5 min for ticarcillin and 76.6 +/- 4.6 min for clavulanic acid. The total clearance of clavulanic acid was 158 +/- 23 ml/min and thus clearly exceeded that of ticarcillin (112 +/- 9 ml/min). The recovery rate in the 24 h urine was 41.3% for clavulanic acid as compared to 79.4% for ticarcillin. Concomitant administration of both substances had little effect on the kinetics of either agent alone. With increasing doses of ticarcillin, a decrease of the non-renal clearance of clavulanic acid was observed. The ratio of the two compounds in serum varied from 25:1 (for 5.2 g Timentin, 15:1 for 3.2 g Timentin) at the time of administration to 59:1 (34:1, respectively) 4 h after infusion.

Adult↗
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↗
PubMed1985

Pharmacokinetics and serum bactericidal activity of ticarcillin and clavulanic acid.

The pharmacokinetics of ticarcillin 5.0 g and clavulanic acid 0.2 g were examined both alone and combined (3.0 or 5.0 g ticarcillin + 0.2 g clavulanic acid as 3.2 or 5.2 g timentin) after a 15 min infusion in ten healthy volunteers. At the same time, the serum bactericidal activity of 5.0 g ticarcillin alone and 5.2 g Timentin was determined against two ticarcillin resistant strains each of Klebsiella oxytoca and Pseudomonas aeruginosa in the first and sixth hour after administration. The serum kinetics of both ticarcillin and clavulanic acid could best be described by an open 2-compartment model. Both substances showed similar kinetic behaviour in serum with a T 1/2 beta of 74.8 +/- 11.5 min for ticarcillin and 76.6 +/- 4.6 min for clavulanic acid. The total clearance of clavulanic acid was 158 +/- 23 ml/min and thus clearly exceeded that of ticarcillin (112 +/- 9 ml/min). The recovery rate in the 24 h urine was 41.3% for clavulanic acid as compared to 79.4% for ticarcillin. Concomitant administration of both substances led to a limited change in the kinetics of both ticarcillin and clavulanic acid. A significant enhancement of the serum bactericidal action of ticarcillin and clavulanic acid was only detected for both Klebsiella species and not for the Ps. aeruginosa species, and only in the first hour.

Adult↗
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↗
PubMed1984

Pharmacokinetics of cefotaxime and desacetyl-cefotaxime in cirrhosis of the liver.

In 9 patients with advanced hepatic cirrhosis and a normal serum creatinine concentration, the pharmacokinetics of cefotaxime (CTX) and its desacetyl metabolite (DACM) were examined in serum and urine after intravenous administration of 2.0 g CTX. The peak serum levels were 130.3 +/- 33.9 and 8.5 +/- 4.6 mg/l for CTX and DACM, respectively. T50% beta was calculated to be 138.1 min (69.3-245.8 min) for CTX. The approximation of the terminal half-life of DACM revealed a prolongation which exceeded 10 h. Accordingly, the AUC amounted to 255.3 +/- 92.0 and 151.9 h X mg/l, respectively. Within 24 h, 62.9% was eliminated in urine as CTX and 19.4% as DACM. The total clearance of CTX was reduced to 164.3 ml/min (58.3-296.6 ml/min), but the renal clearance was only moderately decreased to 90.0 ml/min (24.1-169.3 ml/min). These altered kinetics can be explained by altered metabolic function of the liver as well as by cirrhosis-linked alterations of renal elimination mechanisms.

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

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↗
PubMedDate not supplied

Fluconazole therapy of oral candidiasis in HIV-infected patients: results of a multicentre study.

In an open phase-III study 103 HIV-positive patients with oral candidiasis were treated with oral fluconazole 100 mg/day for 7-21 days (mean 12.2 +/- 6.1 days). Ninety per cent of the patients presented with the full clinical picture of AIDS, in 83% CD4-lymphocytes were < 100/mm3. Clinical and mycological (smear and mouth rinsing) examinations were performed at the start of therapy, after weeks 1, 2, and 3, and at the end of therapy. The clinical findings showed fluconazole therapy to have achieved cure in 71% of the patients and improvement in 16%. Therapy failed in 13%. Mycological tests revealed elimination in 57% and reduction in colony counts in 23% of patients. Therapy failure according to mycological criteria was observed in 20% of all subjects. Adverse events were recorded for 26% of all patients. A causal connection with study therapy was considered as "unlikely" in 20 cases, "questionable" in 17 cases, and "likely" in three cases. Premature discontinuation of fluconazole therapy was required in seven patients, in three of them because of adverse events due to fluconazole. Even in patients with advanced HIV infection and consequently severe immunodeficiency, fluconazole is an important improvement of the therapeutic spectrum.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Dose intensity phase I/II trial with carboplatin, ifosfamide, etoposide and vincristine combined with filgrastim in patients with small-cell lung cancer.

BACKGROUND: The purpose of the study was to evaluate the feasibility of increasing dose intensity by a stepwise reduction of the time intervals between chemotherapy cycles in separate patient cohorts with small-cell lung cancer. Patients received up to 6 courses of combination chemotherapy with carboplatin, etoposide, ifosfamide and vincristine followed by support with filgrastim. Dose intensity, incidence, duration and severity of neutropenic fever and infections, objective response to chemotherapy, and safety of filgrastim were determined. PATIENTS AND METHODS: 29 patients with small-cell lung cancer (limited disease: 2, extensive disease: 27) were treated with a combination of carboplatin 250 mg/m2 i.v. day 1, ifosfamide 2 g/m2 and etoposide 120 mg/m2 i.v. days 1 and 2, etoposide 120 mg/m2 orally day 3, and vincristine 1.4 mg/m2 day 14. Initially, filgrastim (5 micrograms/kg) was administered subcutaneously from day 7 to 16. With shorter treatment intervals, filgrastim was administered on days 4-16 or 4-14. RESULTS: An overall increase in dose intensity by a factor of 1.44 was achieved after reducing the treatment interval from 27 to 17 days. Further reduction to 14 days was not feasible due to persistent thrombocytopenia. Six patients (21%) developed a total of 9 febrile episodes, and 14 patients (48%) had to be withdrawn from the study before the completion of six cycles of chemotherapy. The median duration of infectious episodes was 6 days. Overall, a total of 22 of 27 evaluable patients had an objective response. Longer treatment intervals resulted in a lower probability for objective response (> or = 23 days: 10/14 patients vs. < or = 17 days: 7/7 patients). CONCLUSION: Filgrastim allows for the reduction of treatment intervals in patients with small-cell lung cancer and increased dose intensity with acceptable hematologic and nonhematologic toxicities.

Adult↗