Biomedical subjects

F Jehl

Publications and source records attributed to F Jehl.

At least 109 records · Page 6Linked to original sources

PubMed1988

Pharmacokinetics of teicoplanin in children.

A single dose of 6 mg/kg teicoplanin was infused over 10 min in six children of mean age 7 years, and a single dose of 6 mg/kg was infused over 20 min in four neonates of mean age 8.5 days. Serum sampling was performed at 0 and 10 min and at 1, 4, 12 and 24 h and thereafter 24-hourly, up to ten days. Urine was collected for each 24 h throughout the study in children. Teicoplanin was assayed by high performance liquid chromatography. Tolerability of teicoplanin was excellent both in children and in neonates. For all the patients the serum concentrations of teicoplanin followed an open two-compartment model. Mean Cmax was 48.6 +/- 16.7 mg/l (10 min) in children, and 19.6 +/- 1.05 mg/l (20 min) in neonates, and mean t1/2 beta was 20.5 +/- 5.5 h and 30.3 +/- 6.3 h, respectively. On the basis of the results dosage recommendations for children and neonates are made.

Adolescent↗

PubMed1988

HPLC quantitation of the six main components of teicoplanin in biological fluids.

Teicoplanin, a new glycopeptide antibiotic belonging to the same class as vancomycin, is a mixture of six main components, designated A3, A2-1, A2-2, A2-3, A2-4 and A2-5. An assay method by higher performance liquid chromatography (HPLC) has been devised to separate and monitor each of these components in blood and urine.

Anti-Bacterial Agents↗

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

[Aztreonam treatment of severe infections caused by gram-negative aerobic bacilli].

Twenty nine patients of an intensive care unit (9 women and 20 men), aged 63.9 +/- 15.8 years, with a mean body weight of 62.5 +/- 11.8 kg were treated during 9.4 +/- 2.1 days by aztreonam (2 x 1 g/24 h) administered by short infusion (30 min) for a severe infection due to a Gram-negative bacilli. The primary (n = 25) or nosocomial (n = 4) infection sites were a peritonitis (14), a septicaemia (6), a cholecystitis (6), a pyelonephritis (5), a cholangitis (2), a subphrenic abscess (1) or a pneumonia (2). The isolated Gram-negative bacilli were all susceptible to aztreonam, their MIC being less than or equal to 0.5 micrograms/ml, except for a Pseudomonas aeruginosa (MIC = 4 micrograms/ml). Aztreonam was administered as a single therapy to 7 patients and in association with metronidazole (18) and/or penicillin G (14) to 22 patients; in fact, anaerobes were isolated in ten patients. The mean serum concentrations of aztreonam, as measured by HPLC, before and after the 7th administration respectively were 83.2 +/- 17.5 and 6.1 +/- 5.5 micrograms/ml for peak and through levels. The treatment of the 29 infections was a success in all the cases. No complication occurred due to the presence of Gram positive cocci (n = 4) in the first bacteriological sample, or due to the emergence (n = 12) of Gram positive cocci, except for one case of sepsis of the abdominal wall by Staphylococcus aureus. Aztreonam (2 x 1 g/24 h) may be a suitable alternative for the treatment of severe infections of intensive care units, mostly due to Gram-negative bacilli.

Aged↗

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

Hospital routine analysis of penicillins, third-generation cephalosporins and aztreonam by conventional and high-speed high-performance liquid chromatography.

A high-performance liquid chromatographic procedure for the measurement of fifteen beta-lactam antibiotics in body fluids is described, with special reference to high-speed techniques. The procedure involves a unique sample preparation before analysis for all the following fifteen compounds: benzylpenicillin, ampicillin, cloxacillin, ticarcillin, mezlocillin, azlocillin, piperacillin, cefotaxime and its desacetyl metabolite, cefsulodin, cefoperazone, cefmenoxime, ceftazidime, ceftriaxone and the monobactam aztreonam; thus all biological samples arriving at the laboratory can be treated in batch. Of these fifteen antibiotics, eleven can be chromatographed with the same type of mobile phase, which consists of a mixture of ammonium acetate and acetonitrile in various ratios. Three others need ionpairing chromatography because of their polarity, and ticarcillin requires citric acid. High-speed high-performance liquid chromatography seems to be particularly suitable for the routine analysis of beta-lactam antibiotics because columns equilibrate more rapidly, retention times are much shorter, detection limits are lower and the longer lifetime of columns reduces analysis costs.

Aztreonam↗

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↗

PubMed1987

[Teicoplanin and Gram-positive coccus infections. Results of a multicenter study on 66 cases].

Sixty-six cases of Gram positive infections were treated with teicoplanin in an open multicenter study, comprising 7 centers in Eastern France. There were 38 male patients and 28 females. Teicoplanin was given at a dose of 400 mg daily for a mean duration of 18.4 days. The most common infections were due to Staphylococcus aureus, found in 43 out of 56 documented cases. 69 (89.9%) of the 78 Gram + strains isolated had an MIC for teicoplanin of less than or equal to 2 mg/l. There were 44 serious infections (30 septicemia, 10 endocarditis, 1 joint and bone infection, 2 mediastinitis, 1 toxic shock syndrome) and 22 less serious infections (4 urinary infections, 14 skin and soft tissue infections, 3 lower respiratory infections, 1 hepatic abscess). In 42 cases concurrent medication was given: beta-lactamase in 11 cases, rifampicin in 10 cases, aminoglycosides in 22, phosphomycin in 3, pefloxacin in 5. The clinical cure and improvement rate was 90.10%. Adverse events were reported in 11 patients, and in only 3 cases was the therapy stopped. All were reversible on stopping therapy. Teicoplanin was found to be well tolerated and effective in the treatment of Gram positive infections in this study.

Adolescent↗

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↗

PubMed1987

[Direct determination of clavulanic acid in biological fluids using HPLC].

The so far described HPLC methods for clavulanic acid (CA) monitoring needed post-column derivatization with imidazole, resulting in poorly practicable methods. We propose here a direct determination of CA in human biological fluids with a ion-pairing technology using the bathochromic shift of tetrabutylammonium bromide (TBAB). The separation is performed on a reversed phase analytical column (250 X 4.6 mm) with the following mobile phase: 10% acetonitrile in 1 mM TAB and 20 mM ammonium acetate (pH = 5). The U.V. detection is at 214 nm. Serum and bile are prepared with acetonitrile and methylene chloride, and urines are diluted 1/10 prior the analysis. Retention time of CA is 8.4 min. Detection limit for bile and serum is 0.1 mg/l and 5 mg/l for urines. Within and between-day reproducibility is respectively 5.4% and 7.2% for serum and bile, and 4.7% and 6.8% for urine. This method may be suitable for clinical routine analysis and pharmacokinetic studies.

Bile↗

PubMed1987

[Comparative activity of ticarcillin-clavulanic acid and various beta-lactams against Pseudomonas maltophilia].

An increase is observed in the isolation of P. maltophilia as a casual agent of nosocomial infection, particularly in hospitalized immunocompromised patients. These infections are associated with the acute problem of their treatment as most of the P. maltophilia strains are generally resistant to many of the commonly used antimicrobial agents, including those active against Pseudomonas aeruginosa: beta lactams, aminoglycosides and imipenem. This resistance is correlated with two inducible beta lactamases (L1, pI = 6.9; L2, pI = 8.4). Azlocillin, piperacillin, cefoperazone, ceftazidime, latamoxef, ticarcillin, ticarcillin and clavulanic acid in combination were tested against 93 P. maltophilia isolates by disk diffusion testing and agar dilution technique. The association of clavulanic acid with ticarcillin resulted in better MIC values for ticarcillin (MIC 50 = 32, MIC 90 = 128). 96% of strains were sensible to the breakpoint of 128 mg/l. Other beta lactam antibiotics showed a loss of activity except for latamoxef (67% of strains susceptible to 4 mg/l) which is a potent inhibitor of both beta-lactamases. According to these results, the combination of clavulanic acid with ticarcillin may be useful in the treatment of P. maltophilia acquired hospital infections.

Anti-Bacterial Agents↗

PubMed1987

Ceftazidime: experimental and clinical evaluation of biliary elimination.

During a 3-h perfusion of five isolated rabbit liver preparations, 1.4% of 10 mg of ceftazidime added to the circulating blood was eliminated in the bile and 0.9% was metabolized or inactivated in the liver. Five normal subjects were given 2 g of ceftazidime intravenously; antibiotic concentration in the aspirated duodenal fluid rose progressively during the 4 h of the investigational period to a maximal mean level of 21.3 +/- s.e.m. 9.2 micrograms/ml and 0.05% of the dose given was recovered during this period. The same dose was given to 12 cholecystectomized patients fitted with a Kehr drain. An average peak value of 36.3 +/- 4.0 micrograms/ml was reached in the collected bile during the second hour after drug administration. The 12-h biliary recovery was 0.21% of the dose given. Ceftazidime concentrations in choledochal and gallbladder bile sampled peroperatively in 10 patients 1 h after intravenous administration of 2 g of ceftazidime were 78.3 +/- 12.0 and 17.9 +/- 7.5 micrograms/ml respectively. These data compare favourably with the results of the authors' studies on the biliary elimination of 15 other beta-lactams and are consistent with a possible beneficial effect of ceftazidime in the treatment of biliary tract infections.

Adult↗

PubMed1986

[Evaluation of bile diffusion of piperacillin].

In 10 patients undergoing cholecystectomy peroperative samples of serum, bile and gall bladder tissue were obtained one hour after intravenous injection of 2 g of piperacillin. Measurements were made by high performance liquid chromatography. Mean concentrations of piperacillin were 81.7 +/- 13.6 micrograms/ml in serum (S), 382 +/- 110 micrograms/ml in choledochal bile (CB), 30.8 +/- 8.5 micrograms/ml in gall bladder bile and 10.5 +/- 2.6 micrograms/g of gall bladder tissue. With a CB/S ratio of 4.7, piperacillin may be classified among beta-lactams showing good distribution in the biliary tract. This property would make piperacillin useful against the pathogens usually responsible for biliary tract infections.

Adult↗

PubMed1986

[Experimental and clinical evaluation of the biliary elimination of ceftazidime].

After adding 10 mg of ceftazidime to the circulating blood of five isolated rabbit liver perfusions, total antibiotic excretion over a 3 hours period accounted for 1.4% of the administered dose; only 0.9% was found to be metabolized by the liver. In five healthy subjects given 2 g ceftazidime intravenously, 0.05% (102 +/- 576 micrograms) was recovered in the duodenal fluid over a four-hour period. In 10 patients with a T-tube inserted following cholecystectomy, 0.21% of a 2 g dose of ceftazidime injected intravenously was found in the bile collected over a 12-hour period (4 161 +/- 489 micrograms); a mean biliary peak of 36.3 +/- 4.0 micrograms/ml was recorded during the second hour. In 10 patients in whom serum, choledochal bile and gallbladder bile were sampled simultaneously during surgery 1 hour after IV administration of ceftazidime, the concentrations found were 40.6/e 2.1, 78.3 +/- 12.0 and 17.9 +/- 7.5 micrograms/ml respectively. Our results suggests that ceftazidime may be suitable in the treatment of biliary tract infections.

Adult↗