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Biomedical subjects

K Borner

Publications and source records attributed to K Borner.

At least 91 records · Page 5Linked to original sources
PubMed1985

Biliary elimination of apalcillin in cholecystectomized patients.

Pharmacokinetic examinations were performed in 5 patients with bile-duct drainage following cholecystectomy and choledochus revision with 2 g of apalcillin over 20 min intravenously. In comparison to healthy volunteers they had significantly longer half-life values and long persisting serum concentrations over a period of 24 h. The biliary elimination rate of apalcillin correlated with the hepatic function of the patients and was with 4.3% on the average distinctly lower than that of healthy volunteers, whereby the bile, however, could probably not be collected quantitatively in cases of open papilla. Compensatory excretion of apalcillin took place via the kidneys and, considering the metabolites A1 and A2, it amounted to a total of 73%.

Adult↗
PubMed1985

A study of the penetration of temocillin in the cerebrospinal fluid.

Temocillin concentrations in serum and cerebrospinal fluid (CSF) samples from 8 patients were assayed by high pressure liquid chromatography. It was possible to determine sequential series of ventricular (CSF) and serum concentrations in 4 adult neurosurgical patients with slight to moderate impairment of blood-CSF barriers, because serial CSF samples were obtained from external ventricular drains. In 4 other patients with meningitis, temocillin was given in addition to the regular treatment schedule and 6 'spot' concentrations of temocillin in lumbar CSF and serum samples were determined. Temocillin CSF concentrations in these subjects seemed to be inadequate for the treatment of Gram-positive bacterial meningitis and only partially valuable for the treatment of Gram-negative bacillary meningitis.

Adult↗
PubMed1984

Different mechanisms of TEM-1 and Oxa-1 mediated resistance to piperacillin in E. coli.

Clinical isolates of Oxa-1 and TEM-1 producing strains of E. coli were studied. Susceptibility to piperacillin was determined by the agar and broth dilution procedure, and beta-lactam hydrolysis rates measured by the iodometric method. The beta-lactamases were identified by isoelectric focusing. Our data on TEM-1 producing strains showed a statistically significant correlation between the MIC, if determined by the agar dilution test, and the specific beta-lactamase activity. The majority of Oxa-1 producing E. coli was resistant to piperacillin although the inactivation rate of piperacillin was usually low. Cell wall permeability of TEM-1 producing strains of E. coli to piperacillin was below the lower limit of detectability, but preincubation of the E. coli strains in piperacillin containing broth led to increased cell wall permeability. Bactericidal kinetics of an Oxa-1 and TEM-1 E. coli were studied. It revealed that regrowth of the Oxa-1 strain in piperacillin containing broth was associated with a 25% decrease of piperacillin concentrations without the formation of degradation products, suggesting binding of piperacillin to bacterial cells. The TEM-1 plasmid bearing strain inactivated piperacillin, and the degradation products (penicilloate) could be detected.

Bacteriolysis↗
PubMed1984

Kinetic interactions between azlocillin, cefotaxime, and cefotaxime metabolites in normal and impaired renal function.

Cefotaxime (CTX) kinetics, alone and in combination with azlocillin (AZ), were determined in 18 subjects with either normal or impaired renal function. After the single dose and with increasing renal insufficiency, total CTX clearance fell from 266 to 71 ml/min/1.73 m2. At the same time the terminal t1/2 rose from 1.1 to 2.8 hr. Regardless of the degree of renal function, CTX clearance in combination with AZ in all patients was only 50% to 60% of that with CTX alone. This reduction in total body clearance was due to a parallel decrease in renal and nonrenal clearance. In advanced renal failure, particularly after AZ, the terminal t1/2 of the CTX metabolites increased up to 1000% to 1500% of normal. On the basis of these findings, CTX dosage adjustment is recommended only in patients with a glomerular filtration rate (GFR) below 20 ml/min. After AZ, however, dosage reduction of CTX seems to be advisable at an earlier stage of renal impairment (GFR 40 ml/min).

Adult↗
PubMed1984

Comparative pharmacokinetics of apalcillin and piperacillin.

The pharmacokinetics of apalcillin and piperacillin, each administered intravenously as a single 2-g dose, were compared in 10 volunteers in a randomized study of crossover design using bioassay and high-pressure liquid chromatographic procedures. The concentrations of both penicillins in serum were determined over a period of 12 h and in urine over 24 h. Concentrations of apalcillin and piperacillin at the end of the 15-min infusion were similar; however, at 8 h, concentrations of piperacillin were below measurable levels, whereas concentrations of apalcillin were still measurable at 10 h. Pharmacokinetic parameters were calculated according to a two-compartment open model. The area under the curve and the half-life for apalcillin were larger than for piperacillin. On the other hand, renal clearance of piperacillin was substantially greater than that of apalcillin. Of the apalcillin excreted via the kidneys, approximately one-fifth was eliminated as two microbiologically inactive penicilloic acid derivatives. The nonrenal clearance of apalcillin was 79% of total clearance. Binding of apalcillin to serum protein was almost twice that of piperacillin.

Adult↗
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↗
PubMed1984

Multicentre study of a new enzymatic method of cholesterol determination.

A new enzymatic method for the determination of cholesterol in serum and plasma was evaluated in 8 separate laboratories in comparison with routine and reference methods. Investigation of the analytical reliability in the 2-26 mmol/l measurement range showed the following results: At the set reading points (10 min at 25 degrees C and 5 min at 37 degrees C) the reaction shows complete substrate conversion. The colour complex is stable over a period of 60 min. The response to cholesterol is linear up to 26 mmol/l. Precision within the series was 0.6-2.8% in 20 determinations (coefficient of variation). Day to day precision was 0.5-3.3% in triple determinations of 10 days (coefficient of variation). Accuracy was studied with 2 samples (assigned value: 3.52 and 6.70 mmol/l respectively). In the case of sample 1 the mean for the 8 laboratories was 3.44, with a median of 3.44; for sample 2 the values were 6.68 and 6.72. The results demonstrate an excellent transferability. In comparison with other enzymatic procedures, the values found with the new test were 5-10% higher; these results agree at all concentration ranges with the reference methods of Abell & Kendall and with those from mass spectrometry.

Cholesterol↗
PubMed1983

Determination of cefmenoxime in human body fluids by high-performance liquid chromatography.

A rapid and reliable method for the quantitative determination of cefmenoxime in serum and urine by reversed phase high-performance liquid chromatography is described. Serum was deproteinized with acetonitrile. Urine was diluted with dilute acetic acid (17.5 mmol/l). Separations were performed in isocratic mode using a C18 type column and a precolumn packed with Perisorb RP/8. The eluant consisted of a mixture of acetonitrile and 25.0 mmol/l acetic acid in a ratio of 32/69 (vol/vol). In normal subjects cefmenoxime was well separated from endogenous compounds and various added drugs. Its complete separation was confirmed by selective degradation with beta-lactamase from Bacillus cereus and UV spectrophotometry. The detection limit was 0.3 mg/l at a detection wave-length of 254 nm. Peak areas gave linear results up to concentrations of 500 mg/l. Within-batch precision (coefficient of variation) ranged from 1.1 to 6.2%. Recovery rates varied from 99.0 to 103.3%. Results of a standard microbiological assay correlated well with those obtained by the present HPLC method. Eight healthy volunteers who were given a single intravenous dose of 1 g cefmenoxime excreted 86.3 +/- 5.8% of the unchanged drug within 24 h in urine.

Biological Assay↗
PubMed1983

Serum bactericidal activity and kinetics of azlocillin and moxalactam after single and combined administration.

Ten healthy volunteers received 5 g azlocillin and 2 g moxalactam iv in single and combined administration. Serum and urine concentrations were measured with bioassay and HPLC (high pressure liquid chromatography), and serum bactericidal activity (SBA) was determined at 1 h and 6 h against 6 different clinical isolates. The combined applications of both antibiotics resulted in minor differences in serum kinetics and urine recovery in comparison to single administration. SBAs of both antibiotics against Enterobacteriaceae were between 1:4 and 1:8.4 for azlocillin and between 1:3 and 1:8 for moxalactam after 1 h. The combination of both beta-lactam antibiotics did not result in a decrease in SBA against any strain; rather all Enterobacteriaceae showed a slight increase of SBA at 1 h. It can be concluded from these results that combination therapy with azlocillin and moxalactam has no adverse influence on the pharmacokinetics or the bactericidal activity of either substance.

Adult↗
PubMed1983

Biliary excretion and pharmacokinetics of cefoperazone in humans.

Six patients, 40 to 81 years of age, requiring T-tube drainage of their common bile duct, were studied to assess the biliary tract excretion and pharmacokinetics of cefoperazone. Each patient received 2.0 g of cefoperazone iv over 15 min. Cefoperazone concentrations were determined in serum, urine and bile by means of bioassay and HPLC. The results were compared with a pharmacokinetic study in healthy volunteers. The mean total recovery rate of cefoperazone in urine and bile was with bioassay: 64.5 +/- 15.3% (HPLC: 62.4 +/- 15.5%) in 24 h. 18.6 +/- 14.0% (11.5 +/- 7.1%) were found in the bile and 45.9 +/- 16.2% (50.9 +/- 19.7%) in urine. Peak bile concentrations were 3642 +/- 2975 mg/l (2259 +/- 1337 mg/l) after 2-3 h. The serum levels of cefoperazone showed a slow decrease in patients with a long terminal half life (T1/2 gamma) of 380 min from 295 +/- 90 mg/l initially to 15.9 +/- 11.3 mg/l after 12 h. In normal subjects, serum concentrations decreased much faster (T1/2 gamma = 143.5 +/- 20.0 min) from 232.8 +/- 28.6 mg/l to 1.16 +/- 0.73 mg/l after 12 h. Recovery in urine was 21.4 +/- 5.6%. Using HPLC analysis, we found cefoperazone A in small concentrations in the serum and in higher concentrations in the bile and urine of the operated patients. It is debatable whether cefoperazone A is a true metabolite in vivo or a physical degradation product.

Adult↗
PubMed1983

Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam.

The pharmacokinetics of cefoperazone, cefotaxime, and moxalactam were compared in a cross-over randomized study in 10 healthy volunteers. Each subject received 1.0 g of the three drugs by bolus intravenous injection over 3 min. Serum and urine concentrations were assayed by a microbiological method and in addition by high-pressure liquid chromatography (HPLC) for cefotaxime in five subjects. Maximal concentrations in serum 5 min after the injection were 163 +/- 40.3 mg/liter for cefoperazone, 86.1 +/- 19.0 mg/liter for cefotaxime, and 95.5 +/- 21.1 mg/liter for moxalactam. After 12 h, 1.2 +/- 1.4 mg of cefoperazone per liter and 1.8 +/- 0.9 mg of moxalactam per liter could still be measured. Eight hours after the administration of cefotaxime, serum concentrations were below the detection limit of 0.3 mg/liter in most subjects. By HPLC analysis, the mean maximal concentration of desacetyl cefotaxime was 16.6 +/- 10.5 mg/liter 5 min after application; the metabolite exceeded the serum concentration of the parent compound after 1 to 2 h. Relevant pharmacokinetic parameters were calculated, using two- and three-compartment models. The terminal half-life was 144.1 +/- 37.3 min for cefoperazone, 76.1 +/- 32.0 min for cefotaxime, and 272.4 +/- 114.1 min for moxalactam. The apparent volume of distribution corresponded to the extracellular volume. Only 25.1 +/- 8% of cefoperazone could be detected in urine compared with 53.3 +/- 8.1% of cefotaxime and 61.0 +/- 9.2% of moxalactam in 24 h. A total of 89.6 +/- 11.4% of the cefotaxime dose could be recovered by HPLC in urine, 60.6 +/- 7.7% as cefotaxime and 29.1 +/- 7.0% as desacetyl cefotaxime.

Adult↗
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

Cefotaxime levels in ventricular cerebrospinal fluid, determined by bioassay and by high-performance liquid chromatography.

Five series of cerebrospinal fluid (CSF) samples, obtained from external ventricular drains (EVD) of 4 neurosurgical patients with cefotaxime treatment were tested simultaneously by high-performance liquid chromatography (HPLC) and microbioassay using E. coli V 6311/65 as test organism. Higher cefotaxime (CTX) concentrations in CSF were measured by the microbioassay method in 4 of the 5 series, reflecting the microbioassay being influenced by increasing amounts of desacetyl-cefotaxime (DAC) during the post-application interval. Decrease of CTX levels in CSF was consistently faster in tests performed by HPLC than those using microbioassay. The clinical efficacy in gram-negative bacillary meningitis is to be explained by levels of the parent compound CTX in CSF which are several times higher than the minimal inhibitory concentrations (MICs) of most enterobacteriaceae.

Adolescent↗
PubMed1983

[Candidate selected method for the enzymatic determination of total cholesterol in serum].

An enzymatic method is described for the determination of total cholesterol in serum using a single aqueous reagent which can easily be prepared from commercial substrates and enzymes. The determination is carried out manually, the resulting stable chromogen is measured at a wavelength of 500-550 nm. The cholesterol concentration may be calculated either using a primary cholesterol standard or a constant factor for a given wavelength. The reliability of the method is reported: Data for the imprecision are given on the basis of a survey in 3 laboratories, the accuracy is established by comparison with a definitive and a reference method. Analytical and biological interferances are briefly discussed and results with this enzymatic method are reported concerning the reference values for serum cholesterol.

Cholesterol↗
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↗
PubMed1981

[Determination of triiodothyronine in serum with a heterologous enzyme immunoassay: results of a group survey].

This paper summarises the results of the evaluation of a heterologous enzyme immunoassay in antibody coated tubes for the determination of triiodothyronine (T3) by a group of 11 laboratories. The assay procedure is analogous to an established heterologous thyroxine enzyme immunoassay. The evaluation demonstrated that 1. the specificity of the assay and its analytical range between 0.46 and 9.2 nmol/l meet diagnostic requirements, 2. the intra- and interassay precision was in accordance with that commonly found in radio immunoassays, 3. the recovery of added T3 was between 90 and 103%, 4. the results agreed well with those of self-established radio immunoassays and were comparable with commercial RIA kits, 5. there was no interference by hyperbilirubinaemia or by high concentrations of bile acids, but interference can occur in very haemolytic and lipaemic samples. The great advantage of T3 enzyme immunoassays lies in the absence of restrictions and any authorization needed for working with radioactive substances.

Evaluation Studies as Topic↗