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Biomedical subjects

J M Brogard

Publications and source records attributed to J M Brogard.

At least 55 records · Page 3Linked to original sources
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

Clinical pharmacokinetics of cefotiam.

Cefotiam, a semisynthetic parenteral cephalosporin of the aminothiazole group, exhibits interesting properties: stability against hepatic metabolism and excellent solubility, accounting for an apparent volume of distribution 2 to 3 times higher than that of most other cephalosporins. Its degree of protein binding is about 40%. High concentrations of cefotiam are observed in several tissues (kidney, heart, ear, prostate and genital tract) as well as in fluids and secretions (bile, ascitic fluid). In healthy subjects, the serum elimination half-life is about 1 hour. The pharmacokinetics are linear only for doses lower than 1g. Cefotiam is mostly (and rapidly) eliminated in unchanged form in urine; 50 to 70% of the dose is recovered during the 12 hours following administration, and only severe renal failure, with creatinine clearance less than 5 ml/min, significantly alters the elimination half-life. Although the drug has no proven nephrotoxicity in man, a reduction of the dose is recommended when creatinine clearance is less than 30 ml/min.

Aging↗
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↗
PubMed1989

[Cefpiramide, a new cephalosporin with high hepatic elimination; experimental evaluation of its biliary passage and disposition in the liver].

The biliary elimination and hepatic disposition of cefpiramide were studied using an isolated and perfused rabbit liver model. Five experiments were performed, each lasting 3 hours. After addition of 10 mg of cefpiramide to the circulating blood, the biliary concentration reached a mean peak of 741 +/- 15 micrograms/ml between the 30th and 60th minute; the cumulated biliary elimination of the drug amounted 4042 +/- 1099 micrograms, corresponding to 40.4% of the injected dose. The hepato-biliary clearance was 54.5 ml/hr and the biliary elimination rate constant 0.2019(hr-1). At the end of the perfusion, 21.7% of the dose was still present in the circulating blood and 1.4% is found in the liver. Control experiments showed that 36.2% of the cefpiramide added into the experimental device was submitted to degradation. Thus, it was possible to calculate the rate of liver biotransformation of cefpiramide, which accounted for 0.3%. These experimental results confirm the major role of the liver in the elimination of cefpiramide and prove that the drug is not submitted to hepatic metabolisation.

Animals↗
PubMed1988

High hepatic excretion in humans of cefpiramide, a new cephalosporin.

After intravenous administration of 1 g of cefpiramide, the biliary elimination of the drug was studied by using high-performance liquid chromatography. In five healthy volunteers, a mean peak concentration of 339 +/- 107 (standard error of the mean) micrograms/ml was measured in aspirated duodenal fluid during h 2 after administration, and 1.2% of the dose given was recovered over a 4-h period. A maximal concentration of 1,161 +/- 392 micrograms/ml was reached during h 2 in T-tube bile from 10 recently cholecystectomized patients, with a 24-h biliary recovery of 23.1%; urinary recovery over the same period averaged 49.4%. In 10 patients undergoing cholecystectomy, the concentrations in serum, choledochal bile, gallbladder bile, and gallbladder wall 1 h after cefpiramide administration were 157 +/- 21, 1,726 +/- 501, and 84 +/- 33 micrograms/ml and 23 +/- 4 micrograms/g, respectively. These figures represent the highest biliary concentrations attained so far with a beta-lactam antibiotic and are therefore a good prerequisite for treatment of biliary tract infections with cefpiramide.

Anti-Bacterial Agents↗
PubMed1988

[Evaluation of the biliary excretion of a ticarcillin-clavulanic acid combination in man].

The association of a beta-lactamase inhibitor, clavulanic acid (CA) (0.2 g) to ticarcillin (TIC) (3 g) enhances the activity of the latter on resistant strains. The aim of the present study was to assess their biliary elimination in man. Serum, urine and bile concentrations of TIC and CA were measured in biological samples collected in 10 cholecystectomized patients provided with a T-tube, during 12 hours after the IV administration of 3.2 g of claventin. Concerning TIC, a mean biliary peak of 177 +/- 49 (SEM) micrograms/ml was reached during the 2nd hour; the total biliary output (0-12 h) (AB) was 8.8 +/- 2.6 mg (0.28% of the administered dose), the hepato-biliary clearance CL HB 0.34 ml/min and the biological half-life, TB 1/2 1.2 h. The mean biliary peak of CA was 2.7 +/- 0.5 micrograms/ml and occurred during the first hour. AB amounted to 98.5 +/- 34.7 micrograms (0.04% of dose), CLHB to 0.10 ml/min and TB 1/2 1.2 h. In per-operatively sampled serum, choledochal bile, gallbladder bile and gall-bladder wall, the following concentrations were measured 1 hour after the IV administration of 3.2 g of Claventin. TIC: 105 +/- 11; 386 +/- 66; 72 +/- 20 micrograms/ml and 36 +/- 11 micrograms/g. CA: 3.6 +/- 0.7; 5.9 +/- 1.5; 0.3 +/- 0.3 micrograms/ml and 0.1 +/- 0.1 micrograms/g. The biliary pharmacokinetic profiles allow to favorably consider the prophylactic use of Claventin in the surgery of the biliary tract as well as its therapeutic administration in 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↗
PubMed1988

[The role of ciprofloxacine metabolites in its biliary and urinary elimination in man].

The purpose of the present work was the investigation of the urinary and biliary eliminations of M1, M2, M3 and M4, the four metabolites of ciprofloxacin in twelve recently cholecystectomized patients provided with a T-drain. The four metabolites were measured by HPLC under isocratic conditions for M2 and M4, and by gradient elution for M1 and M3. After a single oral dose of 500 mg of ciprofloxacin, the 24th urinary elimination of the parent compound and its metabolites respectively amounted to 130.1 +/- 15.6; 13 +/- 11; 46.6 +/- 8.2; 13 +/- 3.7 and 0 mg, representing 26.02; 0.54; 1.32; 2.60 and 0% of the administered dose (total: 192.4 mg; 38.5%). During the same investigation period, the biliary elimination respectively reached 1,587 +/- 222; 241 +/- 38; 11,042 +/- 2,489; 144 +/- 51 and 19 +/- 13 micrograms (total: 13 mg) corresponding to 0.32; 0.05; 2.21; 0.03 and 0% (total: 2.61%) of the dose. The urinary and biliary elimination of ciprofloxacin as metabolites respectively represents 12.5 and 2.3% of the dose (total: 14.8%). The important amount of M2 recovered in bile (7 times more than ciprofloxacin itself) let suggest a hepatic biotransformation of ciprofloxacin.

Administration, Oral↗
PubMed1988

Experimental and clinical evaluation of the biliary pharmacokinetic profile of cefpiramide, a new cephalosporin with high hepatic elimination.

Biliary elimination of cefpiramide was studied experimentally and in human subjects using chromatography (HPLC). During a 3-h perfusion of five isolated rabbit liver preparations, 40.4% of cefpiramide added to the circulating blood was eliminated in the bile and only 0.3% was metabolized in the liver. In five healthy subjects, after a single intravenous administration of 1 g of cefpiramide, a maximal concentration of 339 +/- 107 micrograms/ml was reached during the 2nd hour in the collected duodenal fluid, and 1.23 +/- 0.20% of the given dose was recovered within 4 h. In ten cholecystectomized patients provided with a T-tube, intravenous injection of 1 g of cefpiramide resulted during the 2nd hour in a biliary peak concentration of 1161 +/- 392 micrograms/ml. The total amount of antibiotic eliminated in the bile over 24 h averaged 231.5 +/- 39.1 mg, corresponding to 23.2 +/- 3.9% of the administered dose. Hepatic clearance was 3.13 ml/h. Intraoperative specimens sampled simultaneously 1 h after intravenous administration of 1 g of the antibiotic in ten patients undergoing cholecystectomy showed cefpiramide concentrations of 157 +/- 21 micrograms/ml in serum, 1726 +/- 501 micrograms/ml in choledocal bile, 84 +/- 33 micrograms/ml in gall-bladder bile and 22.6 +/- 4.2 micrograms/g in gall-bladder wall. These data emphasize the excellent biliary tropism of cefpiramide, and compare favourably with results concerning 19 other beta-lactams previously studied under the same conditions. They constitute a good prerequisite for possible beneficial treatment of biliary tract infections.

Adult↗
PubMed1988

High biliary elimination of ceftriaxone in man.

Biliary elimination of ceftriaxone was studied in man using chromatography (HPLC). After a single i.v. administration of 2 g of ceftriaxone to 6 normal subjects, a peak concentration of 565 +/- s.e.m. 347 micrograms/ml was reached during the 1st h in the collected duodenal fluid, and 1.4 +/- 0.5% of the given dose was recovered within 4 h. In 10 cholecystectomized patients provided with a T-drain, a maximal biliary concentration of 1,078 +/- 158 micrograms/ml was measured during the 2nd h after i.v. injection of 2 g of ceftriaxone and the 24-h recovery was 9.5 +/- 2.9%. Intraoperative samples obtained in 12 patients undergoing cholecystectomy 1 h after i.v. administration of 2 g of the antibiotic, gave the following results: serum concentration 199 +/- 10 micrograms/ml, choledochal bile = 5,259 +/- 1,085 micrograms/ml, gallbladder bile 4,533 +/- 809 micrograms/ml. These data indicate an excellent biliary elimination of ceftriaxone in comparison with other beta-lactams previously studied under the same conditions and point to be a promising therapeutic potential in biliary tract infections.

Adult↗
PubMed1987

[Ceftriaxone, a cephalosporin with high hepatic elimination. Evaluation of its biliary clearance in man. Therapeutic value].

The biliary elimination of ceftriaxone, a cephalosporin derivative, was quantitatively studied in man with the help of high pressure liquid chromatography (HPLC). In 6 healthy volunteers a mean peak concentration of 565 +/- 347 (SEM) micrograms/ml was observed in the aspirated duodenal fluid within the first hour after i.v. administration of 2 g ceftriaxone, and 1.4 +/- 0.5% of the dose was recovered during the 4 hours investigation period. In 10 cholecystectomized patients provided with a T-drain, the biliary concentration peak (1078 +/- 158 micrograms/ml) was reached within 1 hour after administration and the total 24 hours recovery amounted to 9.5 +/- 2.9% of the dose given. In 12 patients undergoing cholecystectomy, serum, and choledochal (CB) and gallbladder bile (GB) were peroperatively collected 1 hour after i.v. administration of 2 g ceftriaxone; the respective concentrations were: 199 +/- 10 (serum), 5259 +/- 1085 (CB), and 4533 +/- 809 (GB) micrograms/ml. These data point to excellent biliary elimination of ceftriaxone compared with the other beta-lactams previously studied, and afford evidence of its high therapeutic potential in biliary tract infections.

Aged↗
PubMed1987

Biliary elimination of ceftazidime.

When five normal subjects were given ceftazidime 2 g iv, antibiotic concentrations in aspirated duodenal fluid increased progressively during 4 h to a value of 21.2 +/- 9.2 mg/l (mean +/- S.E.M.); 0.05% of the dose given was recovered in duodenal fluid. The same dose was given to 12 patients with an external biliary drain. The mean peak ceftazidime concentration of 36.3 +/- 4.0 mg/l was reached in the collected bile during the second hour after administration. The 12-h biliary recovery was 0.21% of the dose. The respective ceftazidime concentrations in choledochal and gallbladder bile sampled peroperatively in ten patients 1 h after ceftazidime 2 g iv were 78.3 +/- 12.0 and 17.9 +/- 7.5 mg/l. These data compare favourably with the results achieved with other beta-lactam compounds.

Adult↗