Biomedical subjects

F Jehl

Publications and source records attributed to F Jehl.

At least 127 records · Page 7Linked to original sources

PubMed1985

Determination of alpha-amanitin and beta-amanitin in human biological fluids by high-performance liquid chromatography.

A high-performance liquid chromatographic assay of alpha-amanitin and beta-amanitin in human serum, urine, or stomach washings is described. Sample preparation involves a chemical step with deproteinization and organic solvent treatment, and a selective cleanup and concentration step on reversed-phase prepacked cartridges. Separations are performed on a reversed-phase analytical column under isocratic conditions with uv detection at 280 nm. The method allows the quantitation of alpha- and beta-amanitin separately with a detection limit of 10 ng/ml for both toxins.

Amanitins↗

PubMed1985

High-performance liquid chromatographic method for determination of ciprofloxacin in biological fluids.

A simple and precise high-performance liquid chromatographic procedure has been developed for the determination in biological fluids of ciprofloxacin, a new, with extended antibacterial spectrum, quinoline carboxylic acid. The work-up procedure involves a chemical extraction step followed by isocratic chromatography on a reversed-phase analytical column, with ultraviolet detection. The detection limit for blood levels is 10 ng/ml. The calibration curve is linear from this detection limit to 10 microgram/ml. The statistical analysis of the correlation made between this assay and an agar diffusion procedure during a pharmacokinetic study suggests the existence of one or more active metabolites which could be mainly excreted in the bile.

Anti-Infective Agents↗

PubMed1985

[Ciprofloxacine: evaluation of its biliary elimination in man].

To investigate the possibility of therapeutic use of ciprofloxacin in infections of the biliary tract, the serum and bile kinetics, and the biliary, urinary and fecal elimination of this new broad-spectrum quinolone were studied in 12 recently cholecystectomized patients with T-tube drainage. Ciprofloxacin concentrations were determined by simultaneously performed HPLC and microbiological assay in serum, urine, and bile over a 24-hour period following oral administration of a single dose of 500 mg of the drug. The two methods yielded similar values both in the serum and in the urine. Average peak serum concentrations were 0.97 +/- SEM 0.17 microgram/ml (HPLC) and 1.08 +/- 0.19 microgram/ml (microbiological assay) (NS). The respective mean urinary concentrations in the first 6-hour sample were 267 +/- 74 micrograms/ml and 241 +/- 58 micrograms/ml (NS). In bile, however, the microbiological assay gave higher values than HPLC:average peak concentrations of 10.3 +/- 3.4 micrograms/ml and 7.5 +/- 2.8 micrograms/ml (p less than 0.02) respectively, reached during the 2nd hour after drug administration, and mean total 24-hour biliary ciprofloxacin output of 2167 +/- 288 micrograms and 1587 +/- 222 micrograms (p less than 0.01) respectively. This may point to hepatic transformation of ciprofloxacin to more active metabolite(s) than the parent compound. The significantly higher concentrations of ciprofloxacin in bile than in serum exceeded the minimum inhibitory concentration for organisms usually responsible for biliary infections. These infections may, therefore, be favorably affected by ciprofloxacin.

Adult↗

PubMed1985

Determination of vancomycin in human serum by high-pressure liquid chromatography.

A rapid, accurate, reverse-phase high-pressure liquid chromatographic procedure for vancomycin quantitation in human serum, cerebrospinal fluid, and peritoneal fluid was developed. This procedure involves a simple chemical extraction of the antibiotic and is suitable for each of these body fluids. The column and mobile phase used provided a good resolution of the vancomycin peak with a retention time of 6.1 min. The precision of the assay was within the requirement for a daily routine clinical application. Coefficients of variation for within-day reproducibility were 5.80 and 6.28%, respectively, for samples at 50 and 25 micrograms/ml, and for between-day reproducibility they were 11.4 and 11.1%, respectively. No interference was found with respect to beta-lactam and aminoglycoside antibiotics and many other currently used drugs, indicating a good specificity for the procedure. The detection limit of 100 ng/ml has proven to be sufficient for monitoring drug levels in serum obtained after usual dosages. Drug levels in 112 clinical serum specimens assayed by high-pressure liquid chromatography were regressed against the levels obtained for the same samples by radioimmunoassay and fluorescent polarization immunoassay. Correlation coefficients were 0.945 and 0.967, respectively, and were highly significant (alpha less than 0.001).

Bacterial Infections↗

PubMed1985

Comparison of high-pressure liquid chromatography and microbiological assay for the determination of biliary elimination of ciprofloxacin in humans.

Serum kinetics and biliary, urinary, and fecal elimination of ciprofloxacin, a new quinolone derivative, were studied in 12 recently cholecystectomized patients provided with T-tube drainage during 24 h after oral administration of a single 500-mg dose of this substance. Drug concentrations were measured by both high-pressure liquid chromatography (HPLC) and microbiological assay. The results were comparable for the concentrations in serum (average of peaks, 2.0 +/- 0.2 micrograms/ml by HPLC and 2.3 +/- 0.3 micrograms/ml by the microbiological method) and urine (0 to 6 h, 267 +/- 74 and 241 +/- 58 micrograms/ml, respectively). This was not the case for biliary values, for which the microbiological assay yielded significantly higher concentrations than did HPLC (average of peak concentrations, 21.2 +/- 2.6 and 16.0 +/- 2.5 micrograms/ml, respectively [P less than 0.02]), nor for total 24-h biliary output (2,167 +/- 288 and 1,587 +/- 222 micrograms, respectively [P less than 0.01]). This suggests hepatic biotransformation of ciprofloxacin into microbiologically active metabolites. The apparent broad antibacterial spectrum of ciprofloxacin and its higher biliary levels than simultaneously determined serum concentrations suggest that this derivative is suitable for the treatment of biliary tract infections.

Adult↗

PubMed1985

[HPLC, RIA, FPIA. Evaluation of 3 methods for the assay of vancomycin].

We describe a rapid and accurate high performance liquid chromatographic (HPLC) method for vancomycin quantitation. This method is then compared with two immunoassays, RIA and FPIA. The chemical extraction step needed for HPLC is simple and rapid. Both conventional reversed phase HPLC and high speed reversed phase HPLC were tested. The mobile phase was a mixture of aqueous ammonium acetate and acetonitrile. Specificity of the HPLC assay was good. Serum levels in 112 clinical specimens assayed by HPLC were regressed against the levels obtained for the same samples by both RIA and FPIA. The correlation was good (RIA : r = 0.945; FPIA : r = 0.967). Considering the disadvantages of RIA, HPLC and FPIA emerge as the methods of choice.

Chromatography, High Pressure Liquid↗

PubMed1984

[HPLC study of the pharmacokinetics of mezlocillin administered by 30-minute infusion and comparison with the direct intravenous route].

Mezlocillin pharmacokinetics were investigated in eighteen patients from a surgical service after a 30 minutes infusion with the purpose, on one hand, to compare this way of administration with a bolus intravenous infusion, and on the other hand to confirm or invalidate capacity-limited dose-dependent pharmacokinetics. Dosages were 2 g (n = 8) and 5 g (n = 10). Mezlocillin levels were measured by high performance liquid chromatography. Calculated data obtained with the 30 minutes infusion are different from those resulting from a bolus infusion. Peak levels, alpha and beta are lower ; T 1/2 beta, areas under the curve, and distribution volumes are higher. Most of the calculated data were not in agreement with a capacity-limited kinetic at the two studied dosages. The two regression-lines (2 g and 5 g) of mezlocillin body clearance versus creatinine clearance superimpose exactly. The 30 minutes infusion, and important hemodynamic variations between our 18 patients may partly explain the differences between our data and those published in the literature.

Adult↗

PubMed1983

[Focus and value of the assay of 5 beta-lactams using high-performance liquid chromatography].

Severe infectious diseases treatment often needs a frequent antimicrobial agent blood levels control. These controls are still performed by microbiological assay procedure. High performance liquid chromatography (HPLC) is now allowing a new kind of assay procedure and improves on speed, specificity and sensitivity. We developed a procedure allowing us to monitor every day by routine, five beta-lactam antibiotics with only one analytical column: benzylpenicillin, ampicillin, cloxacillin, mezlocillin and cefotaxime. A single extraction procedure suitable to the five beta-lactam antibiotics and to various body fluids and the use of three mobile phases, permit us to give a quick answer to the clinicians and thus to consider a rapid adaptation of the doses being administered. In consideration of the specificity, it is possible to control blood levels of each beta-lactam antibiotic even by associated antimicrobial treatment, what is sometimes impossible using the microbiological assay procedure. Cefotaxime is well separated from its active metabolite desacetyl-cefotaxime. The disparity of the levels obtained, for the same posology, essentially by prematures and new-borns, but also in case of massive infusions for endocarditis justify the use of a rapid and specific procedure like high performance liquid chromatography (HPLC).

Anti-Bacterial Agents↗

PubMedDate not supplied

Piperacillin and netilmicin combination therapy for febrile episodes in neutropenic patients.

We assessed the efficacy of a piperacillin (3 x 4 g/d) and netilmicin (5 mg/kg/d) combination therapy for infections in febrile neutropenic patients. The study was conducted over a 30-month period and 203 patients were included. Bone marrow transplant recipients were not included in this study. Origin of infection was documented in 101 (50%) episodes: 33 fungal, viral or parasitic infections and 68 bacterial infections mainly composed of septicemia. Of the 169 evaluable patients with proved bacterial infections or non-documented infections, 129 (76%) recovered with the piperacillin and netilmicin combination treatment. All gram-positive bacterial infections failing first line therapy were cured after the addition of vancomycin. Piperacillin and netilmicin appeared very effective in this large monocentric prospective study. It does not seem necessary to include vancomycin in first line therapy of infections of the neutropenic patients in our institution; however, vancomycin must be added early in the case of suspected or documented staphylococcal infection failing empiric treatment.

Acute Disease↗

PubMedDate not supplied

Investigation of the biliary clearances of cefotaxime and desacetylcefotaxime by an original procedure in cholecystectomised patients.

The biliary elimination of cefotaxime (CTX) and its metabolite desacetylcefotaxime (DSCTX) were measured by HPLC in nine recently cholecystectomised patients following the i. v. injection of 15 mg/kg body weight of CTX. All of the bile was collected by an original procedure: the inflated balloon of a Fogarty catheter was introduced into the distal branch of a Kehr drain T-tube. Biliary clearance of CTX and DSCTX was measured for 8 h. Cefotaxime peaked at 90 min after injection at 34.5 +/- 15.3 mg/l; in the 7-8 h sample it was 2.7 +/- 1.7 mg/l. DSCTX peaked at the same time at 49.3 +/- 17.0 mg/l, and was 4.6 +/- 3.2 mg/l at 8 h. The bile/serum ratio of CTX and DSCTX concentrations was above 1 from the first to the eighth hours (range: 1.35 +/- 1.08 to 11.0 +/- 3.1). The biliary clearance of CTX was 0.190 ml/min. The total amounts of CTX and DSCTX eliminated in bile were respectively 1050 +/- 472.8 micrograms and 1902.7 +/- 804.1 micrograms (0.093 +/- 0.041% of the dose and 0.186 +/- 0.077% of the dose). Considering the minimum inhibitory concentration of the pathogens currently encountered in biliary sepsis, CTX should be a suitable antimicrobial agent for the treatment of biliary infections.

Adult↗

PubMedDate not supplied

Pharmacokinetics of a new oral formulation of amoxicillin.

The bioavailability of the recently developed 1 g dispersible tablet form of amoxicillin (B) and the 1 g dispersible tablet in suspension form (C) were compared to that of the 1 g standard reference formulation (A). Twelve healthy volunteers were involved in this single-dose, open, randomized, three-way cross-over study. The mean peak serum levels were 14.1 +/- 4.1 micrograms/ml after A, 15.1 +/- 3.1 micrograms/ml after B and 15.1 +/- 5.4 micrograms/ml after C. The area under the drug concentration versus time curves were 47.6 +/- 12.0 micrograms.h/ml after A, 52.8 +/- 10.2 micrograms.h/ml after B and 51.1 +/- 13.8 micrograms.h/ml after C. On the basis of these two pharmacokinetic parameters, the three formulations were found to be bioequivalent. In addition, the predicted serum concentrations during multiple dosing (3 times a day), derived from the corresponding mean concentrations after a single 1 g dose of C showed that 8 hourly administration would yield therapeutic serum concentrations for infections such as uncomplicated community-acquired pneumonia due to susceptible or less susceptible strains in otherwise healthy subjects.

Administration, Oral↗

PubMedDate not supplied

Ciprofloxacin biliary disposition in cholecystectomised patients with special references to HPLC and bioassay data.

The biliary disposition of ciprofloxacin was studied in 12 recently cholecystectomised patients during 24 hours following a single oral administration of 500 mg of the drug. Ciprofloxacin was measured in serum, urine, bile and faeces by both high performance liquid chromatography (HPLC) and bioassay. The results were found to be comparable for the concentrations in serum (mean Cmax = 0.97 +/- 0.17 microgram/ml by HPLC and 1.08 +/- 0.19 microgram/ml by bioassay) and in urine (0.6 h: 267 +/- 74 micrograms/ml and 241 +/- 58 micrograms/ml respectively). Higher concentrations were found in bile when measured by bioassay compared with HPLC (peak concentration = 10.3 +/- 3.4 micrograms/ml and 7.5 +/- 2.8 micrograms/ml respectively; p less than 0.02). The total biliary elimination was also significantly higher according to bioassay data (2167 +/- 288 micrograms/ml versus 1587 +/- 222 micrograms/ml; p less than 0.01). This suggests a first pass effect and hepatic biotransformation of ciprofloxacin to one or more active metabolite (s).

Administration, Oral↗

PubMedDate not supplied

Penetration of roxithromycin into gingival tissue.

Roxithromycin is a new macrolide with an antibacterial spectrum similar to that of erythromycin. Absorption is rapid and complete, resulting in high serum levels and a long half-life. Tissue distribution is extensive and sustained, as shown by the high concentrations measured in the lung, prostate, ovaries, liver, kidney, and skin. In this study, we measured the penetration of roxithromycin into gingival tissue at steady state in 30 patients treated orally with 150 mg every 12 hr for 5 days. Tissue specimens were sampled at 2, 4, 6, 8, or 12 hr (n = 6 each time) after dose 10, and blood samples were taken simultaneously. Serum and tissue concentrations of roxithromycin were measured by high-performance liquid chromatography. The peak serum level, reached 4 hr after dosing, was 6.60 +/- 1.15 micrograms/ml. The peak tissue level was 4.63 +/- 1.84 micrograms/g and was reached after 8 hr. From 4 to 10 hr after dosing, tissue concentrations were greater than 2 micrograms/g, that is, higher than the MIC90 of roxithromycin against most oral pathogens. These data support the use of roxithromycin in the treatment of oral infections.

Absorption↗

PubMedDate not supplied

Corynebacterium group D2 ("Corynebacterium urealyticum") constitutes a new genomic species.

Twenty-one Corynebacterium group D2 ("C. urealyticum") strains were found to constitute a tight DNA hybridization group distinct from named Corynebacterium species. The strains of Corynebacterium group D2 had cell wall component type IV, short chain mycolic acids and G+C content of DNA of 65-66 mol %. Corynebacterium group D2 constitutes a genomic species which can be identified by phenotypic tests.

Base Composition↗

PubMedDate not supplied

[Biliary excretion of cefotaxime and desacetylcefotaxime].

The biliary excretion of cefotaxime (CTX) and its metabolite desacetylcefotaxime (DSCTX) was measured by HPLC in 9 recently cholecystectomized-patients following the IV injection of 15 mg/kg body weight of CTX. The totality of bile was collected by an original procedure: the inflated balloon of a Fogarty catheter was introduced into the distal branch of a Kehr drain T-tube. Biliary clearance of CTX and DSCTX was measured for 8 h. Cefotaxime peaked at 90 min. after injection at 34.5 +/- 15.3 micrograms/ml; in the 7-8 h sample it was 2.7 +/- 1.7 micrograms/ml. DSCTX peaked at the same time at 49.3 +/- 17.0 micrograms/ml, and was 4.6 +/- 3.2 micrograms/ml at 8 h. The bile/serum ratio of CTX and DSCTX concentration was 1 from the 1st to the 8th hours (range: 1.35 +/- 1.08 to 11.0 +/- 3.1). The biliary clearance of CTX was 0.190 ml/min. The total amounts of CTX and DSCTX eliminated in bile were respectively 1050 +/- 472.8 micrograms and 1902.7 +/- 804.1 micrograms (0.093 +/- 0.041 p. 100 of the dose and 0.186 +/- 0.077 p. 100 of the dose). Considering the minimum inhibitory concentration of the pathogens currently encountered in the biliary sepsis, CTX should be a suitable antimicrobial agent for the treatment of biliary infections.

Adult↗

PubMedDate not supplied

In vitro time-kill curves of cefepime and cefpirome combined with amikacin, gentamicin or ciprofloxacin against Klebsiella pneumoniae producing extended-spectrum beta-lactamase.

Extended-spectrum beta-lactamases (ESBLs) are found in numerous Enterobacteriaceae, mainly in Klebsiella pneumoniae. We investigated the pharmacodynamics of two new extended-spectrum cephalosporins, cefepime and cefpirome, alone and combined with either amikacin or gentamicin or ciprofloxacin by means of time-kill curves against ESBL-producing, aminoglycoside-resistant K. pneumoniae. When used alone, cefepime (8 and 16 mg/l) resulted in a 2 and 3 log decrease at 6 h, respectively, but at 24 h regrowth occurred. The combination of cefepime (8 mg/l) with amikacin (4 mg/l) resulted in a 4 log decrease at 6 h, but there were no surviving bacteria at 6 h when combined with amikacin (8 mg/l). The combination of cefepime (16 mg/l) with gentamicin (4 mg/l) resulted in a 4 log decrease in 24 h. The antimicrobial combination of cefepime (32 mg/l) with ciprofloxacin (2 mg/l) resulted in a 4 log decrease in 24 h. Cefpirome (8 mg/l) induced a 2 log decrease at 4 h; 32 mg/l cefpirome resulted in a 3 log decrease followed by regrowth at 24 h. The regrowth observed in the late phase with cefpirome alone disappeared when combined with aminoglycoside. When cefpirome (32 mg/l) was used in combination with ciprofloxacin (1 mg/l), it resulted in a 4 log decrease in 24 h.

Amikacin↗

PubMedDate not supplied

Ocular penetration kinetics of fosfomycin administered as a one-hour infusion.

The penetration of fosfomycin in aqueous humour was studied in 21 patients who were to undergo cataract surgery. All patients received 4 grams of fosfomycin as an infusion lasting one hour. Concentrations of the drug in aqueous humour were measured 1, 2, 4, 6 and 12 hours after the start of infusion. Drug concentrations in aqueous humour and serum were measured by HPCE (High Performance Capillary Electrophoresis). The aqueous humour concentration at one hour was 11.46 mg/l +/- 2.12. Peak concentration was 14.63 mg/l +/- 5.54, reached two hours after the infusion. Concentrations were high until 6 hours and remained significant at 12 hours. These results confirm the excellent diffusion of fosfomycin in aqueous humour, with high levels at 12 hours. They justify its use in intraocular infections, by infusions repeated every eight hours, to maintain concentrations above the MIC 90 for organisms usually susceptible to the drug.

Adolescent↗

PubMedDate not supplied

[Determination of enoximone and its principle metabolite in serum and urine using high pressure liquid chromatography].

We developed a high performance liquid chromatography method for the monitoring of enoximone and its main metabolite in serum and urine. Samples handling involves a unique chemical extraction step by ethylacetate. Serum needs at first to be deproteinized by acetonitril. The chromatographic separation is realized on a reversed phase analytical column by gradient elution with acetonitrile. Quantification is by U.V. absorbance at 365 nm. We compared our new method with the method so far considered as reference one. When specificity, accuracy and linearity of both procedures are similar, we greatly enhanced the detection limit [(5 ng/ml for (E) and (SE)] and the practicability: ease of use, rapidity and lower cost.

Cardiotonic Agents↗