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Biomedical subjects

G Humbert

Publications and source records attributed to G Humbert.

At least 91 records · Page 5Linked to original sources
PubMed1987

[Pharmacokinetics of habekacin in patients with chronic renal insufficiency].

Pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic were investigated in six healthy subjects and twenty-five uraemic patients (six of whom were on hemodialysis) after a single 3 mg/kg Im or IV administration. After the IM injection, the peak serum levels were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. Elimination serum half-life increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearance below 10 ml/min. Renal impairment did not significantly modify the apparent volume of distribution. After a single 3 mg/kg dose as one hour-IV infusion in six hemodialysis patients, elimination half-life averaged 48 h and 5 h, out of and on a 4 to 5 hour-hemodialysis session, respectively. Habekacin pharmacokinetic parameters appeared to be similar to those of the other available aminoglycoside antibiotics.

Aminoglycosides↗
PubMed1987

[Diffusion of 5-fluorocytosine in bronchial secretions in patients with respiratory insufficiency].

The 5-Fluorocytosine bronchial secretion levels of 14 patients with a chronic respiratory disease were determined using a microbiological method. The mean maximal concentrations (7.76 +/- 7 micrograms/ml) were obtained at the end of a single 25 mg/kg i v perfusion over 30 minutes. The level increased when five i v perfusions were performed every 6 hours and bronchial diffusion was higher and faster by concomitant administration of (bromhexin hydrochloride). Therefore, 5-Fluorocytosine was not found in bronchial secretions of four patients in spite of a normal serum levels (21.5 +/- 5 micrograms/ml).

Bronchi↗
PubMed1986

Pharmacokinetics of cefonicid in uraemic patients.

Eight subjects with normal renal function and 20 uraemic patients with various degrees of renal insufficiency were given a single iv dose of 1.0 g cefonicid, as a bolus injection. Five groups of subjects were studied: group I, GFR greater than 80 ml/min, group II 30 less than GFR less than 80 ml/min, group III 10 less than GFR less than 30 ml/min, group IV GFR less than or equal to 10 ml/min and group V, haemodialysis patients. Cefonicid concentrations in plasma and urine were measured by microbiological assay (MA) and HPLC method. Results were similar with the two techniques. The mean peak plasma levels were 200-300 mg/l and the apparent volume of distribution was 0.18-0.20 1/kg for all patients. The elimination half-life (T 1(2) beta) increased as renal function decreased: 5.31 +/- 1.30 h in healthy subjects and 58.92 +/- 12.38 h in patients with end-stage renal disease. Urinary elimination of cefonicid was inversely related to the degree of renal impairment: 83% of the dose in 24 h in normal subjects and 13.6% of the dose in patients with severe renal failure. Total body clearance decreased from 23.9 +/- 3.4 ml/min/1.73 m2 (group I) to 1.9 +/- 0.2 ml/min/1.73 m2 (group V). Renal clearance fell from 19.0 +/- 4.9 ml/min/1.73 m2 (group I) to 1.0 +/- 0.4 ml/min/1.73 m2 (group IV). The fractional clearance and the non renal clearance were similar in normal subjects and in uraemic patients. Cefonicid is not haemodializable because of its high protein binding. Dosage of cefonicid should be adjusted according to the degree of renal impairment. Supplemental doses are not necessary after haemodialysis.

Adult↗
PubMed1986

[Urinary excretion of phospholipids: index of aminoglycoside nephrotoxicity].

Aminoglycosides have a low molecular weight and bind weakly to proteins. They are easily filtered through the glomeruli, bind to phospholipid receptors located on the brush border of proximal tubule cells, and penetrate within the cells by endocytosis. Aminoglycosides decrease lysosomal A and C phospholipase and sphingomyelinase activities. This impairs the degradation of phospholipids, with formation of abnormal intralysosomal structures called myeloid bodies as a result. These myeloid bodies are gradually eliminated from the cells into the lumen of the tubule and excreted in the urine. We studied the urinary excretion of phospholipids following 1, 3, 5 and 10 days of treatment with gentamicin (3 mg/kg/day) or tobramycin (3 mg/kg/day) in patients with acute pyelonephritis. Infection-free, non-treated subjects were used as controls. Patients with a urinary tract infection treated by a quinolone made up a third group. Urinary N-acetyl-beta-D-glucosaminidase (NAG), an indicator of epithelial necrosis, was also evaluated. Results were expressed per ml urine, per mg creatinine and per 24 hours. Only the results expressed per mg creatinine appeared valid. No significant increase in serum creatinine or urinary NAG was found in patients under gentamicin. In the patients with a urinary tract infection not treated with an aminoglycoside, urinary phospholipid excretion on D1 was decreased as compared to controls (p less than 0.01). Urinary phospholipid excretion was never found to be increased in patients under aminoglycosides. No significant difference was found between males and females. Mistaken interpretations occurred if urinary excretion of phospholipids or NAG was not expressed per mg creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Group R streptococci: wild boars as a second reservoir.

Group R streptococci have caused many cases of septicaemia and meningitis in patients handling live or slaughtered pigs which were the only known reservoir of group R streptococci. A human case, due to a wild boar, is reported here and it is therefore concluded that there exist both a domestic (pig) and a wild (wild boar) reservoir of group R streptococci.

Adult↗
PubMed1984

Pharmacokinetic study of cefmenoxime (SCE 1365-CMX) in healthy adults.

Cefmenoxime pharmacokinetics were investigated in six healthy volunteers after intravenous and intramuscular administration of 0.5, 1, and 2 g. Blood and urine samples were analyzed by reversed-phase high-pressure liquid chromatography using ultraviolet detection at 275 nm. The assay is precise and linear up to 200 micrograms/ml-1, with 0.02 micrograms/ml-1 as the limit of detection. Linearity of cefmenoxime kinetics was demonstrated because the area under the plasma concentrations is proportional to studied doses. Eight hours after 1 g of cefmenoxime intramuscularly, mean plasma concentrations are, respectively, 0.6 +/- 0.1 and 0.3 +/- 0.1 microgram/ml-1. Intramuscular cefmenoxime is rapidly absorbed (Ka = 7.28 hours-1) with complete bioavailability (F = 0.99); apparent volume of distribution is 0.35 liters/kg-1 and elimination half-life 1.5 hours. The fraction of cefmenoxime excreted unchanged in the urine after intramuscular administration is 0.72, indicating a major contribution of renal clearance in total clearance. Experimental data after intramuscular administration were well fitted with a two-compartment model.

Adult↗
PubMed1984

[Pharmacokinetics of azlocillin in chronic renal failure and hemodialysis patients].

The pharmacokinetics of azlocillin were studied in 16 patients with varying degrees of renal impairment (creatinine clearance Ccr ranging from 0 to 52 ml/min/1.73 m2) and on and off sessions in 4 of these patients on periodical haemodialysis. A single dose of azlocillin 80 mg/kg was given by intravenous infusion over 30 min. Maximum concentrations in the sera of patients with renal impairment were the same as in normal subjects, ranging from 300 to 400 micrograms/ml. The elimination half-life (t 1/2) increased as renal function deteriorated, with values of 1.11 h in subjects with healthy kidneys to 5.66 h in patients with Ccr less than 15 ml/min (maximum 8.38 h). The apparent volume of distribution (Vd) was unchanged in patients with renal impairment but was significantly increased in patients on haemodialysis. The mean percentage of the dose administered excreted in the urines decreased from 60-70% in normal subjects to about 11% in patients with severe renal failure, but urinary concentrations remained above therapeutic levels. The extra-renal elimination of azlocillin was unmodified by renal impairment. Azlocillin is easily removed by dialysis: t 1/2 values between and during 6 h sessions of haemodialysis were 6.55 h and 2.81 h respectively, corresponding to a 45.8% extraction on the dialyser. These results are comparable to those found in the literature and can be used as a basis for adjusting azlocillin dosage to the degree of renal function.

Adolescent↗
PubMed1984

[Pseudomonas aeruginosa meningitis treated with azlocillin. 5 cases].

Prior to the introduction of new beta-lactam antibiotics, such as ureidopenicillins and some third generation cephalosporins, the choice of antibiotics for the treatment of meningitis caused by Ps. aeruginosa was limited, and even now, this infection remains of poor prognosis. Five patients with meningitis, aged from 18 to 75 years, were treated with azlocillin. The strains of Ps. aeruginosa isolated were all sensitive to azlocillin, the zones of inhibition being greater than 20 mm in diameter with bacteriostatic concentrations. Azlocillin was administered 8-hourly by intravenous injection in doses of 30 g/day in 3 cases and 15 g/day in 2 cases. The mean duration of treatment was 33 days (range 23-50 days). In addition to azlocillin 4 patients received an aminoglycoside (tobramycin or amikacin) parenterally and, in one case, intrathecally. Four patients underwent a surgical operation on the focus of infection between the 9th and 13th days of treatment. In 3 of these 4 patients surgery was necessary to obtain apyrexia, but in all cases the CSF was already sterile when it was performed. The outcome was favourable in all 5 cases. One patient relapsed on 4 occasions due to persistent petrous bone fistula; each time, the azlocillin treatment was reinstituted and brought about clinical and bacteriological cure. The germ was eradicated in CSF on the 3rd day of treatment in 3 patients and on the 7th day in one. One patient developed transient eosinophilia and another, transient neutropenia after 30 days. It is concluded that azlocillin, associated with an aminoglycoside, is an active and effective antibiotic for the treatment of Ps. aeruginosa meningitis.

Adolescent↗
PubMed1984

Metronidazole kinetics in patients with acute renal failure on dialysis: a cumulative study.

Nine patients with acute renal failure who were undergoing dialysis at intervals depending on clinical state were injected with metronidazole, 7.5 mg . kg-1 iv every 8 hr. Plasma samples were drawn during the 8 hr after the first infusion, during the first dialysis session, and during the course of the fourth infusion after the first three dialysis sessions. Metronidazole and its two main metabolites (alcohol [M1] and acid [M2]) were assayed by HPLC. The plasma t 1/2 of metronidazole (6.8 hr) is of the same order as that in healthy subjects. M1 and M2 plasma levels increased continuously until the next infusion. Dialysis clearances of metronidazole and its metabolites were about 60 ml . min-1; 25% of metronidazole in the body at the beginning of hemodialysis was eliminated. The corresponding apparent t 1/2 s are 3.3 hr (metronidazole), 8.0 hr (M1), and 7.9 hr (M2). In patients with acute renal disease under hemodialysis, there was no cumulation of metronidazole and its metabolites; hence there is no need for change in dosage regimen.

Acute Kidney Injury↗
PubMed1984

Concentrations of cefotaxime and the desacetyl metabolite in serum and CSF of patients with meningitis.

Thirty-two cases of meningitis (20 caused by Gram-positive or -negative cocci, 7 by Gram-negative bacilli or listeria, and 5 with aseptic meningitis) received cefotaxime, 2 g 8-hourly, in addition to routine therapy. The concentrations of cefotaxime and its desacetyl metabolite in serum and CSF were determined by a high pressure liquid chromotography. Mean concentration of cefotaxime in CSF ranged from 0.8 mg/l (aseptic meningitis), to 6.4 mg/l (Gram-negative and listeria meningitis), and from 0.5 to 5.4 mg/l for the metabolite. The concentrations of both cefotaxime and the derivative demonstrated a correlation with the degree of inflammation (i.e., cell count and protein concentration) and were higher at 3 h after an infusion of antibiotic than at one and two hours. The concentration showed no marked decline on day 10 when signs of inflammation had largely resolved. The concentrations of both the parent compound and the metabolite 3 h after the infusion suggest that, considering the activity and half life of both the dosing might be spaced at 6-8 h intervals.

Cefotaxime↗
PubMed1984

Pharmacokinetics of ceftazidime in normal and uremic subjects.

The pharmacokinetics of ceftazidime, administered as a single intravenous dose of 15 mg/kg given in a bolus injection over 3 min, were investigated in 5 normal subjects and in 19 uremic patients. The subjects studied were divided into five groups according to values for endogenous creatinine clearance (CLCR): group I, five subjects with CLCR greater than 80 ml/min; group II, five patients with CLCR = 30 to 80 ml/min; group III, six patients with CLCR = 10 to 30 ml/min; group IV, four patients with CLCR = 2 to 10 ml/min; and group V, four anuric patients on hemodialysis. A two-compartment open model was used to calculate the pharmacokinetic parameters. In normal subjects, the mean apparent elimination half-life was 1.57 +/- 0.13 h. The central distribution volume and the apparent volume of distribution were 0.127 +/- 0.023 and 0.230 +/- 0.015 liter/kg, respectively. Of the injected dose, 83.6 +/- 3.6% was eliminated in the urine as parent drug within 24 h. The terminal half-life increased with impairment of renal function to about 25 h in severely uremic patients. Impairment of function did not significantly modify the half-life at alpha phase, central distribution volume, or apparent distribution volume. A 6- to 8-h hemodialysis procedure reduced concentrations of ceftazidime in plasma by approximately 88%, and the elimination half-life was 2.8 +/- 0.2 h. There was no evidence of accumulation of ceftazidime in four patients with severe and chronic impairment of function who received doses of 0.5 to 1.0 g every 24 h for 10 days.

Adult↗
PubMed1983

[Pharmacokinetics of moxalactam in adults].

Specific characteristics of Moxalactam, a new beta-lactam antibiotic, are high serum concentrations, prolonged half-life and good tissular diffusion. After IM injection of a single dose of 0.25, 0.5 and 1 g, the maximum serum concentration, achieved at one hour, averages 13, 16-21 and 30-50 micrograms/ml. After rapid IV injection of 0.5 and 1 g, the average maximum serum concentrations are 90 and 150 micrograms/ml; after an IV infusion of 2 g over 20 minutes, maximum concentrations are 150 to 180 micrograms/ml. Moxalactam elimination kinetics are linear, independent from the dose and route of administration, with a distribution half-life (T 1/2 alpha) between 0.20 and 0.60 hours and an elimination half-life (T 1/2 beta) between 2 and 2.5 hours (range: 1.9 and 3.1 hours). The apparent distribution volume is between 15 and 18 liters, i.e. 20 to 25% of the body weight. Serum or total clearances and renal clearances are respectively 80 to 100 and 50 to 90 ml/mn, with wide variations from one author to another. Approximately 70 to 90% of the administered dose are eliminated in the urine over 24 hours, without any tubular secretion. Renal failure results in a progressive increase of the elimination half-life, which can reach 20 hours in patients with anuria; approximately 50% of the injected dose are recovered by hemodialysis. Many pharmacokinetic studies have demonstrated the excellent diffusion of the agent in the various tissues and body fluids, particularly in the CSF. From the collation of bacteriologic and pharmacokinetic data, dosage regimens adjusted to the renal function can be proposed.

Adult↗