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H Lode

Publications and source records attributed to H Lode.

At least 253 records · Page 14Linked to original sources
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

Perioperative antibiotic prophylaxis in bile-duct interventions: results of two prospective randomized studies.

The success of perioperative prophylaxis in gallbladder surgery was examined in two prospective randomized studies with a total of 326 patients. Postoperative wound-healing impairments did not occur in any of the patients receiving a single preoperative application of an antibiotic with a high biliary elimination rate (ceftriaxone or apalcillin). 11% of a control group without prophylactic antibiotic application evidenced infectious wound-healing disturbances.

Adolescent↗
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

[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

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↗
PubMed1985

Antimicrobial therapy in dialysis patients. II. Remaining antibiotics and antimicrobiologic agents.

Antimicrobial therapy in hemodialysis patients is made possible by pharmacokinetic dosage modifications. The problem is that overdosage produces side effects whereas therapeutic drug action is missed by underdosage. The dose should be calculated to achieve identical peak levels (for bactericidal drugs) as in normal renal function or identity of AUC (for bacteriostatic drugs). Antimicrobial therapy is started with a loading dose which usually equals the dose in patients with normal renal function. The maintenance dose is reduced in renal failure and adjusted to the increase in the dominant elimination half-life. The effect of hemodialysis must be taken into account and replacement of the removed fraction by a supplementary dose is needed to assure therapeutic drug action.

Aminoglycosides↗
PubMed1985

Antibiotic infection prophylaxis in gallbladder surgery--a prospective randomized study.

In the course of 1 year, 180 patients undergoing elective surgery for confirmed cholelithiasis were included in a prospective randomized study in which they either received 2 g of preoperatively applied ceftriaxon intravenously at the beginning of anesthesia or, as an alternative, no antibiotic at all. Infectious wound-healing disturbances occurred postoperatively in 11% in the control group and in no case in the prophylaxis group. The difference is statistically significant.

Adolescent↗
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↗