Search PubMed⌕ Search

Biomedical subjects

G Humbert

Publications and source records attributed to G Humbert.

At least 73 records · Page 4Linked to original sources
PubMed1991

Influence of rifampin on the pharmacokinetics of pefloxacin.

Pefloxacin and rifampin are frequently associated in the antibiotic therapy of deep-seated, and especially bone-located, infections. The influence of rifampin, a potent drug metabolism enzyme inducer, on the pharmacokinetics of pefloxacin was studied in a randomized crossover trial involving eight young healthy male volunteers. Every volunteer received either pefloxacin alone (period A) or pefloxacin after a 10-day induction by rifampin (period B) given as a 900 mg daily oral dose, and both periods were separated by a 3-week washout period. During both periods, pefloxacin was given during 3 days as a 400 mg b.i.d. oral dose (six doses) followed by a 400 mg intravenous dose on the fourth day. The kinetics of pefloxacin are significantly influenced by rifampin: The minimum (12-hour) plasma concentration, area under the concentration-time curve, and elimination half-life decreased respectively from 4.26 +/- 1.57 to 2.70 +/- 1.00 mg/L, 78.91 +/- 22.82 to 57.81 +/- 16.69 mg.hr/L, 14.46 +/- 3.46 to 10.08 +/- 2.44 hours (p less than 0.05). The renal clearance of pefloxacin was unchanged, but the plasma clearance increased from 94.04 +/- 39.04 to 126.82 +/- 47.36 ml/min (p less than 0.05). The plasma clearance of N-demethyl and N-oxide metabolites were similar for both periods, but the cumulative renal excretion (0 to 96 hours) decreased significantly (p less than 0.01) for period B versus period A. This definite but moderate inductive effect of rifampin on the pharmacokinetics of pefloxacin does not suggest a dose modification of pefloxacin in therapeutic association with rifampin, but pefloxacin assay in plasma seems to be advisable.

Adult↗
PubMed1991

Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings.

The amoxicillin-clavulanate combination (Augmentin) frequently induces gastric complaints and diarrhea by an unknown mechanism. The aim of this study was to assess the effects of two orally therapeutic regimens of amoxicillin-clavulanate on small bowel motility in human beings. Duodeno-jejunal manometric recordings were performed in six healthy subjects treated in a cross-over double-blind study with placebo; amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h for 3 days; or amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h on day 3 only (1-day regimen). Recordings were all performed on day 3 during a diurnal fasting period, a fed state after a standard dinner, and a nocturnal fasting period. Amoxicillin-clavulanate did not affect the motility of the small intestine during the diurnal fast or the fed state. During the nocturnal fast, amoxicillin-clavulanate significantly increased the motility index of the nonpropagated contractions and tended to increase the duration and the amplitude of the propagated contractions. The same digestive motor effect was already observed on the first day of treatment (1-day regimen). This study demonstrates that the oral administration of a therapeutic regimen of amoxicillin-clavulanate is associated, in most cases, with the occurrence of small intestinal motor disturbances.

Adult↗
PubMed1990

Pharmacokinetics of quinolones in renal insufficiency.

The pharmacokinetics of the new fluoroquinolone derivatives have been extensively studied in patients with various degrees of chronic renal insufficiency during the last few years. Their kinetic profiles depend on the elimination pathways and on the degree of metabolic transformation. Renal insufficiency does not significantly modify pefloxacin kinetics. For the other new quinolones, a decrease in glomerular filtration rate below 20-30 ml/min induces an increase in terminal half-life and a decrease in plasma and renal clearance, related to the degree of renal impairment. These drugs are poorly removed by haemodialysis. Dosage adjustments are required, particularly in severe renal failure and for the drugs almost exclusively excreted, in unchanged form, via the renal route.

Anti-Infective Agents↗
PubMed1990

Lomefloxacin pharmacokinetics in subjects with normal and impaired renal function.

Lomefloxacin pharmacokinetics were investigated in 6 normal subjects and 24 uremic patients after a single oral dose of 400 mg. In subjects with normal renal function, the peak level in plasma averaged 3.5 +/- 0.9 micrograms/ml (mean +/- standard deviation) and was obtained at 1.3 +/- 0.9 h. The absorption rate constant was 3.8 +/- 1.6 h-1. The terminal half-life was 7.77 +/- 0.95 h. The apparent volume of distribution was 2.54 +/- 0.66 liters/kg. Total body and renal clearances were 259 +/- 83 and 200 +/- 55 ml/min per 1.73 m2, respectively. The percentage of the dose recovered unchanged in 48-h urine was 80.6 +/- 2.8. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 38 h in severely uremic patients (glomerular filtration rate, less than 10 ml/min). Renal insufficiency did not significantly modify the peak level in plasma, the time to peak, the apparent volume of distribution, or the nonrenal clearance of lomefloxacin. The dialysis clearance of lomefloxacin was 54 +/- 13 ml/min. Linear relationships were found between lomefloxacin pharmacokinetic parameters and glomerular filtration rate data. Dosage adjustments are necessary in uremic patients.

4-Quinolones↗
PubMed1989

[Preventive treatment of infection caused by gram-negative bacteria using anti-lipopolysaccharide antibodies. Evaluation in patients with aplasia].

The prophylaxis of severe Gram-negative infections with human antiserum to lipopolysaccharide (LPS) was evaluated in a randomised study of 60 patients with therapeutic aplasia for leukaemia. The antiserum was found to be ineffective in preventing Gram-negative infections. The levels of anti-LPS antibodies showed that passive immunization was obtained in only one half of the patients. These disappointing results warrant further investigations to evaluate the effectiveness of this prophylactic treatment.

Adult↗
PubMed1989

Neurological manifestations of Lyme disease and treatments.

Lyme disease is a multi-systemic infection due to B. burgdorferi, with neurological manifestations observed in its second and third stages. Except for the suggestive triad meningitis--radiculoneuritis--facial palsies, the diagnosis is often difficult because of the pleiomorphism of neurological manifestations. These can be localized or diffuse, with central involvement, meningitis or peripheral manifestations. Past history, cerebrospinal fluid (CSF) examination, immuno-assays for specific antibodies in serum and especially CSF are helpful in diagnosis. Betalactam antibiotics (penicillin G, amoxicillin, and third generation cephalosporins) are the most effective treatment with good results in the early and acute stages of neurological disease.

Anti-Bacterial Agents↗
PubMed1988

[Pharmacokinetics of ceftazidime in healthy and renal failure subjects].

Ceftazidime is poorly bound to plasma proteins, is not metabolized and is excreted mostly by glomerular filtration. Its elimination half-life is about 1.5-2 hours, and their kinetics are modified by renal impairment. The dosage recommended in adult is 1 to 2 g 8-hourly, to be adjusted to the needs of individual cases. The interval between doses must be extended to 12 hours in patients with mild renal impairment and to 36-48 hours in those with severe renal failure. A supplementary dose of ceftazidime is required at the end of each haemodialysis session. In patients under chronic peritoneal dialysis, the loading dose (10 mg/kg) is followed by continuous administration of 5 mg/kg into each dialysis cavity.

Ceftazidime↗
PubMed1988

Efficacy of pefloxacin-fosfomycin in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.

The efficacies of pefloxacin, fosfomycin, and both of these agents in combination against methicillin-resistant Staphylococcus aureus were assessed in a rat endocarditis model. The combination prevented emergence of the fosfomycin and pefloxacin resistance seen in 36 and 4%, respectively, of animals receiving either agent alone and was more effective than either agent in sterilizing cardiac vegetations.

Animals↗
PubMed1987

Ofloxacin pharmacokinetics in renal failure.

The pharmacokinetics of ofloxacin were investigated in 12 normal subjects and 21 uremic patients after the administration of a single oral 200-mg dose. An open three-compartment body model was used to calculate ofloxacin pharmacokinetic parameters. In healthy subjects, the peak plasma level averaged 2.24 +/- 0.90 micrograms/ml and was obtained at 0.83 +/- 0.31 h. The absorption rate constant was 4.22 +/- 1.64 h-1. The terminal half-life was 7.86 +/- 1.81 h. The apparent volume of distribution was 2.53 +/- 0.78 liters/kg. Total body and renal clearances were 241.4 +/- 53.8 and 196.5 +/- 42.9 ml/min per 1.73 m2, respectively. A total of 68.4 +/- 11.9% of the dose was recovered unchanged in 24-h urine. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 37 h in severely uremic patients. Renal insufficiency did not significantly modify the peak plasma level, the apparent volume of distribution, the fractional clearance, or the nonrenal clearance of ofloxacin. However, the time to peak level was delayed in patients with creatinine clearance of less than 30 ml/min. Linear relationships were found between ofloxacin pharmacokinetic parameters and glomerular filtration rate data. Ofloxacin is only very slightly removed by hemodialysis. Dosage adjustments of ofloxacin in uremic patients are proposed.

Adult↗
PubMed1987

Pharmacokinetics of habekacin in patients with renal insufficiency.

The pharmacokinetics of habekacin, a new semisynthetic aminoglycoside antibiotic, were investigated in six healthy subjects and 25 uremic patients (six of whom were on hemodialysis) after administration of a single 3-mg/kg dose. Six healthy subjects received the 3-mg/kg dose both intramuscularly (i.m.) and intravenously (i.v.) (1-h infusion). Uremic patients were given the 3-mg/kg dose as an i.m. injection, except for the hemodialysis patients, who received the dose as a 1-h i.v. infusion. After the i.m. injection, the peak concentrations in serum were higher and the times to peak levels were longer in patients with renal impairment than in healthy subjects. The elimination half-life in serum increased in relation to the degree of renal impairment, from 2 h in normal subjects to 32 h in patients with creatinine clearances of less than 10 ml/min. Renal impairment did not significantly modify the apparent volume of distribution. After the same 3-mg/kg dose as a 1-h i.v. infusion in six hemodialysis patients, the elimination half-life averaged 48 and 5 h off and on a 4- to 5-h hemodialysis session, respectively. The habekacin pharmacokinetic data appeared to be similar to those of the other available aminoglycoside antibiotics.

Adult↗