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M Dorner

Publications and source records attributed to M Dorner.

At least 19 recordsLinked to original sources
PubMed1992

[Biliary excretion and hepatic disposal of cefixime: experimental and clinical study].

Cefixime is a new oral cephalosporin with in vitro activity similar to that of third-generation cephalosporins. Renal excretion accounts for only 40% of systemic clearance of cefixime, suggesting that biliary excretion of the drug may be significant. This study was designed to determine to what extent nonrenal clearance of cefixime is due to biliary excretion of the parent compound. In an isolated perfused rabbit liver model, biliary excretion of cefixime was very low, with only 0.28 +/- 0.15% of a single 10 mg dose injected in the system being recovered in the bile after three hours perfusion. The liver biotransformation rate for cefixime was found to be 16.2%. These results are in striking contrast with those obtained in human studies. Cefixime levels in duodenal juice aspirates collected over four hours following an intravenous injection of 200 mg cefixime in six healthy volunteers were at least fivefold concomitant serum levels. Studies of bile collected by external biliary drainage during 24 hours following an oral dose of 200 mg cefixime in ten cholecystectomized patients showed that the Cmax was 56.9 +/- 70 mg/l, i.e., 25-fold the serum Cmax (2.3 +/- 0.85 mg/l). The bile AUC/serum AUC ratio was 20.4 +/- 20.3. Mean bile level of cefixime was still as high as 4.3 +/- 3.7 mg/l 20 hours after dosing. The amount of cefixime excreted in the bile over 24 hours was 10.0 +/- 12.3 mg i.e., 5% of the dose administered. Twenty-four hour renal excretion of cefixime was 53.3 +/- 26.2 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

[Experimental study on the hepatobiliary kinetics and excretion of temafloxacin. Evidence for production of active metabolites by the rabbit liver].

Temafloxacin is a new fluoroquinolone derivative currently under evaluation. Its hepatobiliary disposition remains undefined as yet. The present study represents an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for three hours with reconstituted and oxygenated blood in a closed circuit. A the onset of the procedures, temafloxacin 10 mg were added to the circulating blood. Both bile and blood were sampled throughout the perfusion time, and liver fragments were taken at the end of the experiments. Temafloxacin levels were measured by HPLC in serum and hepatic tissue, and by both HPLC and microbiological assay in bile. The percentage of drug undergoing hepatic biotransformation appeared to be high, i.e. 58.3%. This finding is substantiated by the comparison of temafloxacin levels in bile, as provided by HPLC and microbiological assay, the latter yielding concentrations twice as high (biliary peak: 33.5 +/- 2.8 micrograms/ml versus 19.3 +/- 3.1 micrograms/ml by HPLC assay) as those obtained by HPLC (p less than 0.05). Consistently, the average amount of temafloxacin excreted into the bile (0-3 h) was, respectively, 92 micrograms (0.9% of the dose) and 204 micrograms (2.0%) as determined by HPLC and microbiological methods (p less than 0.05); this statistically significant difference suggests the presence of active metabolites in bile. The presented results bring out evidence for substantial biotransformation of temafloxacin by Rabbit liver. Extrapolation to other species, however, would be hazardous; further pharmacokinetic studies are needed in order to assess the relevance of these findings in humans.

4-Quinolones↗
PubMed1990

Biliary elimination and hepatic disposition of a new fluoroquinolone, temafloxacin: experimental evaluation.

Temafloxacin is a new quinolone derivative presently under evaluation. Its pharmacokinetic profile, and particularly its biliary elimination and hepatic disposition, remains undefined. The present study describes an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for 3h (h) with reconstituted blood in a closed circuit; 10 mg of temafloxacin were added to the circulating blood at the onset of the procedure. Bile was recovered throughout the experiments and liver fragments were taken at the conclusion. Assays were carried out by high-performance liquid chromatography. Pharmacokinetic analysis was performed with reference to a monocompartmental open model. Under these conditions, the serum half-life of temafloxacin was 3.1 and the maximal biliary concentration of 19.3 +/- SEM 3.1 micrograms/ml was reached between 30 and 60 min; the cumulative biliary elimination (0-3 h) amounted to 92 +/- 16 micrograms (0.9% of the added dose). Total and hepatobiliary clearances were calculated as respectively 134 and 2.38 ml/h and the hepatobiliary elimination rate as 0.0042 (h-1). At the end of the procedure, 25.7 +/- 3.5% of the added dose of temafloxacin was still present in the circulating blood, and 13.7 +/- 2.4% in the liver. Degradation of the antibiotic in the perfusion device concerned only 2.4% of the dose. The percentage of temafloxacin undergoing hepatic biotransformation, determined by subtraction, was high (57.3%). Under these experimental conditions, temafloxacin appears to be particularly stable in serum, poorly eliminated as parent compound in the bile, highly fixed in the liver and above all subject to a probable hepatic biotransformation. Extrapolation of these experimental data to other species or to the whole organism would be hazardous, but these results should stimulate studies on a possible hepatic metabolism of this new trifluoroquinolone in man.

4-Quinolones↗
PubMed1990

Biliary pharmacokinetic profile of piperacillin: experimental data and evaluation in man.

The purpose of the present experimental and clinical work is to revisit the biliary pharmacokinetic properties of piperacillin. Whereas the up to now published data result from microbiological assays, this work was realized by high performance liquid chromatography. In the isolated and perfused rabbit liver model (n = 5; 3 h), the biliary level peaked at 1,013 +/- 305 micrograms/ml between 30 and 60 min. During the experiments, 56.7% and 10.8% of the administered piperacillin (10 mg) were respectively eliminated in bile and submitted to hepatic biotransformation. In man, a single 2 g i.v. dose was administered to 6 volunteers. The excretion measured in the duodenal fluid was 1,681 +/- 601 micrograms in 4 h (0.08% of the administered dose). In cholecystectomized patients (n = 10) provided with a T-drain, the biliary peak concentration was 211 +/- 64 micrograms/ml during the 2nd h, and the 24 h biliary elimination was 12,963 +/- 3,332 micrograms, representing 0.65% of the administered dose. The hepato-biliary clearance was 0.80 ml/min. On per-operatively collected serum, choledocal bile, gallbladder bile and gallbladder wall samples (n = 10 patients), the concentrations of piperacillin simultaneously measured 1 h after the i.v. administration of 2 g were respectively, 81.7 +/- 20.5, 382 +/- 110, 30.8 +/- 2.5 micrograms/ml and 10.5 +/- 2.6 micrograms/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Biliary elimination and hepatic disposition of piperacillin: experimental evaluation].

The rate of biliary elimination and the hepatic disposition of piperacillin were studied by using an experimental model of a three hours perfusion of five isolated rabbit liver preparations. After addition of 10 mg of the antibiotic to the circulating blood, a mean biliary peak of 1,013 +/- 305 micrograms/ml was obtained between the 30th and 60th minute. The cumulated biliary elimination (0-3 hr) amounted to 5,665 +/- 389 micrograms (56.7% of the dose given). The hepatobiliary clearance was calculated to 134.2 ml/hr and the biliary elimination rate constant to 0.5 545 (h-1). After the procedure, 7.2 +/- 2.7% of the dose of piperacillin was still present in the circulating blood and 0.4 +/- 0.1% in the liver. The degradation of the antibiotic in the perfusion device concerned 24.9% of the dose. The percentage of piperacillin undergoing hepatic biotransformation, calculated by subtraction, was 10.8%. Under these conditions, the biliary elimination of piperacillin is much higher than that of the twenty other beta-lactams studied in our laboratory by the same experimental procedure.

Animals↗
PubMed1989

Biliary elimination of ticarcillin plus clavulanic acid (Claventin): experimental and clinical study.

The aim of the present study was to assess the biliary elimination and disposition of Claventin, a combination of clavulanic acid (CA), a beta-lactamase inhibitor, with ticarcillin (TIC), resulting in an enhancement of the activity of the antibiotic and broadening of its antibacterial spectrum. This work was done experimentally and in humans. Assays of both molecules were performed by HPLC. During a 3 h perfusion of five isolated rabbit liver preparations, 1.3 +/- 0.2% and 0.4 +/- 0.1% of TIC and CA added to the circulating blood were eliminated in the bile. At the same time, 31.8% of TIC and 50.5% of CA were submitted to a hepatic biotransformation. In healthy subjects (n = 5), after a single i.v. injection of 3.2 g of Claventin (TIC: 3 g + CA: 0.2 g) mean peak concentrations of 66.8 +/- 31.9 micrograms/ml (TIC 4th h) and 0.3 +/- 0.1 microgram/ml (CA, 2nd h) were observed in the aspirated duodenal fluid where 0.07% and 0.01%, respectively, of the administered dose were recovered during the 4 h investigation period. In cholecystectomized patients (n = 10) provided with a T-tube, i.v. administration of Claventin, 3.2 g, resulted in biliary maximal levels of 177 +/- 49 micrograms/ml (TIC: 2nd h) and 2.7 +/- 0.5 microgram/ml (CA 1st h). Total amount of each derivative eliminated in bile over 12 h averaged 0.28% (TIC) and 0.05% (CA) of the given dose. Hepatobiliary clearance was 20.5 ml/h (TIC) and 4.4 ml/h (CA). In intra-operative simultaneously sampled specimens of serum, choledochal bile, gallbladder bile and gallbladder wall, the following concentrations were measured 1 h after i.v. administration of Claventin: TIC: 105 +/- 10; 386 +/- 66; 72 +/- 20 micrograms/ml and 36 +/- 11 micrograms/g, CA: 3.5 +/- 0.7; 5.9 +/- 1.5; 0.3 +/- 0.3 microgram/ml and 0.1 +/- 0.1 microgram/g. The biliary pharmacokinetics determined in humans makes it possible to consider favourably the prophylactic use of Claventin in surgery of the biliary tree and constitute a good prerequisite for a possible beneficial treatment of biliary tract infections.

Adult↗
PubMed1988

[Polymorphism of C4 and factor B in type I diabetes].

The haplotypic frequencies of the fourth component of complement (C4) and factor B (Bf) have been determined in 44 Alsatian type 1 diabetics. An increased frequency of the rare allele Bf F1 (9.1% vs 1.5%) and of the silent alleles of C4 (C4 AQO: 21.6% vers 15.5% -C4 BQO: 29.6% vs 16.0%) was observed in diabetics in comparison to the general population of the same geographic area. A complete HLA haplotype determination has been obtained in 24 type 1 French diabetics. Three haplotypes were associated with the diabetic susceptibility: HLA-A30 CW5 B18 BfF1 C4A3BQO DR3 (18.75% vs 0.86%), HLA-A1 CW7 B8 BfS C4AQOB1 DR3 (15.58% vs 4.17%), HLA-A2 CW3 BW62 BfS C4A3B3 DR4 (6.25% vs 0.45%). The authors suggest that the silent alleles of C4 could modulate the expression of the diabetic susceptibility genes by lowering of the serum C4 hemolytic activity.

Alleles↗
PubMed1987

[Experimental evaluation of the biliary tract passage of ceftriaxone and its hepatic disposition].

The biliary elimination of ceftriaxone was studied by an isolated perfused rabbit liver model (n = 5). After adding of 10 mg of this antibiotic to the circulating blood of this preparation, a mean biliary peak level reaching 120.5 +/- 24.6 micrograms/ml was obtained between the 30th and 60th minutes. The total amount of ceftriaxone eliminated unchanged in the bile collected during a 3h period represents 8.8 +/- 2.6% of the administered dose. At the end of this study period, 32.7 +/- 3.3% of the initial dose remained in the circulating blood. The hepatic tissue concentrated 3.7% of the whole dose. At last, control experiments proved that 36.4% of the added antibiotic has been degraded by the experimental system itself. Thus the remaining 18.4% can be attributed to a hepatic biotransformation of ceftriaxone.

Animals↗
PubMed1986

[Current trends in dietetics in diabetology and their experimental bases].

The last decade has witnessed drastic changes in our views on diet for diabetics, whether insulin-dependent or not. To bring blood glucose levels down to normal values, thereby preventing diabetic microangiopathy or alleviating its course, remains the compelling purpose of treatment, but the modalities and constraints of the dietetic measures which contribute to this result have been radically revised. Leaving aside fashions and controversies, three tendencies have emerged: the low carbohydrate diet does not improve the glycaemic balance but implies an excessive fat intake which may aggravate the microangiopathy. Of course, an hypocaloric diet remains fundamental in the management of obese non-insulin dependent diabetics; the effects on glycaemia of the carbohydrate ration constituents must be reconsidered. The classical distinction between "fast" and "slow" sugars seems to be excessive and insufficient, if not erroneous. Food replacements must take into account the glycaemic index; a minimal dietary fibre intake has a favourable effect on post-prandial glycaemia and lipid metabolism and is to be recommended, notably to diabetics.

Diabetes Mellitus↗
PubMed1986

Biliary elimination of cefotiam, an experimental and clinical study.

Five isolated rabbit livers were in vitro perfused over a 3-hour period. After addition of 10 mg of cefotiam to the circulating blood, a biliary peak concentration of 76.2 +/- 14.2 micrograms/ml (mean +/- SEM) was reached between the 90th and 120th min; 3.1 +/- 0.4% of the dose given was excreted in the bile during the 3-hour period. In 10 recently cholecystectomized patients provided with a T-tube drain, 1 g of cefotiam was given intravenously. A biliary peak concentration of 340 +/- 81 micrograms/ml was observed 2 h later. 1.8 +/- 0.7% of the administered dose was recovered in the bile during the 12-hour period. In 5 clinically normal subjects given intravenously 1 g of cefotiam, 0.5 +/- 0.2% of the administered dose was found in the duodenal fluid aspirated over a 4-hour period. Cefotiam concentrations measured in choledochal and gallbladder bile collected simultaneously during operation 1 h after intravenous administration of 1 g of the drug to 10 patients were 502 +/- 102 micrograms/ml and 143 +/- 39 micrograms/ml, respectively; they exceeded significantly the concentration determined in the serum sampled at the same time (17.9 +/- 2.6 micrograms/ml). The biliary parameters of cefotiam were compared with those of 14 other beta-lactam antibiotics previously studied by the same procedure. The results of the present study are consistent with a possible beneficial effect of cefotiam in the treatment of biliary tract infections.

Animals↗
PubMed1986

[Malnutrition and deficiency of insulin secretion in alcoholic cirrhosis. Study by the assay of urinary C-peptide].

In order to evaluate the relationship between nutritional status and insulin secretion in cirrhosis, the following parameters of caloric (tricipital skin fold, prealbumin) and proteic (arm muscle size, transferrin, 24 h-urinary creatinine excretion) nutritional status were compared in 20 alcoholic cirrhotics and 10 normal subjects. Insulin secretion was evaluated in both groups by insulin and C-peptide response to an intravenous glucose tolerance test and by 24 h urinary excretion of C-peptide. When compared to normals, cirrhotics have lower values for all nutritional status parameters and individually for at least three of those in 14 (70 p. 100) patients. In cirrhotics there is a significant decrease of the 4-min poststimulative response of insulin and C-peptide, contrasting with higher basal and late poststimulative values than in normals. This contrast could be explained by a reduced metabolic clearance rate of insulin (consistent with insulin resistance) and of C-peptide (the urinary clearance of which is 2.5 times lower in cirrhotics than in normals). The 24-h urinary excretion of C-peptide, probably weakly dependent of this reduced clearance, is 50 p. 100 lower in cirrhotics: 12.9 +/- 1.6 nM/24 h than in normals: 26.0 +/- 2.4 nM/24 h (p less than 0.001). In cirrhotics there is a significant linear correlation between 24 h urinary C-peptide excretion and all the nutritional status parameters but one (prealbumin). These results indicate that in cirrhosis: 1) urinary C-peptide excretion rate is a good index of insulin secretion; 2) urinary C-peptide indicates a marked deficit in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Biliary elimination of apalcillin: an experimental and clinical study.

After adding 10 mg of apalcillin to the circulating blood of five isolated rabbit liver perfusion preparations, total apalcillin biliary recovery over a 3 h-period accounted for 30.7% of the administered dose; the biliary peak level averaged 686.0 +/- 135.9 micrograms/ml. In five healthy subjects, a maximum level of 1088 +/- 582 micrograms/ml was measured in the duodenal fluid collected during 4 h following intravenous injection of 1 g of apalcillin. In 10 cholecystectomized patients provided with T-tube drainage, after the same dosage, a biliary peak of 2093 +/- 859 micrograms/ml was attained in the 3rd hour and cumulative biliary recovery over a 12 h-period amounted to 12.1% of the injected dose. In 20 patients undergoing biliary surgery, intra-operative simultaneous sampling performed 1 h after intravenous injection of 1 g of apalcillin showed antibiotic levels of 65.5 +/- 5.0 micrograms/ml in serum, 3860 +/- 551 micrograms/ml in common bile duct bile and 2552 +/- 627 micrograms/ml in gallbladder bile. The results of these investigations were compared with data previously obtained with 13 other beta-lactam derivatives.

Ampicillin↗
PubMed1985

Biliary elimination of beta-lactam antibiotics by the isolated perfused rabbit liver.

Biliary elimination of 15 beta-lactams was studied using a model of isolated perfused rabbit liver. During the perfusion period, the main liver functions were well preserved. The highest biliary concentrations were reached by antibiotics of the penicillin group, and the highest biliary recovery was observed with metampicillin, apalcillin and mezlocillin (46.5, 30.7 and 20.3%, respectively, of the dose administered). This technique was also suitable for estimating the degree of bio-transformation in the liver of the antibiotics studied.

Animals↗
PubMed1985

[Biliary excretion of apalcillin. Experimental study and evaluation in man].

Biliary excretion of apalcillin, a new derivative of the ureido-penicillin group, was investigated both experimentally and in humans. After adding 10 mg of this antibiotic to the circulating blood of an isolated rabbit liver perfusion model (n = 5), mean total apalcillin biliary recovery (0-3 h) accounted for 30.7% of the administered dose; the biliary peak averaged 686.0 +/- 135.9 micrograms/ml. In 5 healthy subjects, a mean maximum level of 1088 +/- 582 micrograms/ml was measured in the duodenal fluid collected during the 4 hours following an i.v. injection of Ig of apalcillin. In 10 cholecystectomized patients provided with T-tube drainage, after the same dosage, a mean biliary peak of 2093 +/- 859 micrograms/ml was reached at the third hour and cumulative biliary recovery of apalcillin over a period of 12 hours amounted to 12.1% of the injected dose. In 20 patients, undergoing biliary tract surgery, intra-operative assays performed 1 hour after i.v. injection of 1 g of apalcillin, showed simultaneous mean antibiotic activity of 65.5 +/- 5.0 micrograms/ml in serum, 3860 +/- 551 micrograms/ml in main duct bile and 2552 +/- 627 micrograms/ml in gallbladder bile. The results of these investigations were compared with data previously obtained under identical procedures with 13 other beta-lactam derivatives.

Ampicillin↗
PubMed1984

[Insulin-dependent diabetes with acute onset. Remissions induced by early temporary blood glucose normalization].

Within 6 months of the acute onset of an insulin-dependent diabetes, remission of insulin-dependence was attempted in 30 hospital patients by strict control of glycaemia obtained in a few days with intravenous infusions of insulin, using a macropump. This was followed by an oral antidiabetic treatment, and the patients were considered in remission when metabolic control was achieved. By this method remission of insulin-dependence was obtained in 90% of the patients; it lasted for more than 1 year on average, and its degree seemed to depend on the time elapsed between the clinical onset of the disease and the beginning of the intravenous treatment but also, to a lesser extent, on the residual secretory capacity of the pancreas when this treatment was instituted. Thus, an intensive metabolic control increases the effectiveness of an oral treatment as regards both number of patients improved and duration of remission. When administered alone at the onset of the disease the oral treatment is only effective in about 30% of the cases.

Adolescent↗
PubMed1984

[Biosynthetic human insulin. Pharmacokinetic characteristics and activity in normal subjects].

The pharmacokinetics and pharmacodynamic effects of intravenously injected (0.06 U/kg) human biosynthetic insulin of recombinant DNA origin and purified porcine insulin, both regular, were compared in 10 healthy volunteers. Both had identical immunological properties. Some of their pharmacokinetic features, such as total plasma clearance and bioavailability, were similar, but they appeared to differ in biological half-life, elimination rate constant and apparent volume of distribution. No appreciable difference was found between their hypoglycaemic activity and their inhibitory effect on endogenous insulin secretion. However, hyperglucagonaemia seemed to be less pronounced after human biosynthetic insulin than after purified porcine insulin. These findings are discussed by comparison with the results of other studies on human biosynthetic insulin.

Adult↗