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Biomedical subjects

F Faurisson

Publications and source records attributed to F Faurisson.

31 records · Page 2Linked to original sources
PubMed1993

Efficacy and ocular penetration of sparfloxacin in experimental streptococcal endophthalmitis.

Gram-positive cocci are the most common pathogens in severe human eye infections. Streptococcal endophthalmitis is a devastating infection, and intravitreal antibiotic therapy is limited by retinal toxicity. Because few systemic antistreptococcal antibiotics penetrate into the vitreous, sparfloxacin, a newer quinolone with improved antistreptococcal activity, might be of interest. We therefore assessed its efficacy by the intravitreal route in a rabbit model of streptococcal endophthalmitis. The vitreal bacterial count (mean +/- standard deviation log10 CFU per milliliter) was significantly reduced after an intravitreal injection of 800 micrograms of sprafloxacin (4.9 +/- 0.7) relative to the counts in untreated control (7.1 +/- 0.7) and pefloxacin-treated (7.8 +/- 1.2) eyes. After systemic administration to rabbits, the maximum concentration of sparfloxacin in serum was 5.6 micrograms.ml-1 and the half-life was 7.5 h. Sparfloxacin exhibited very good penetration ratios in the vitreous (54%), cornea (76%), and lens (36%). In the vitreous, the levels of sparfloxacin remained greater than the MICs for most gram-positive cocci for up to 18 h. Further experimental studies are warranted to determine the efficacy of systemic sparfloxacin as adjuvant therapy in the treatment of human endophthalmitis.

Animals↗
PubMed1992

A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. The French Study Group on Selective Decontamination of the Digestive Tract.

BACKGROUND: Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation, and the procedure is used widely in Europe. However, it is unclear whether selective decontamination improves survival. METHODS: We conducted a randomized, double-blind multicenter study in which 445 patients receiving mechanical ventilation in 15 intensive care units were given either prophylactic nonabsorbable antibiotics (n = 220) or a placebo (n = 225). Topical antibiotics (tobramycin, colistin sulfate, and amphotericin B) or a placebo was administered through a nasogastric tube and applied to the oropharynx throughout the period of ventilation. The main end points were the mortality rate in the intensive care unit and within 60 days of randomization. RESULTS: A total of 142 patients died in the intensive care unit; 75 (34 percent) in the treatment group and 67 (30 percent) in the placebo group (P = 0.37). Mortality within 60 days of randomization was similar in the two groups (P = 0.40), even after adjustment for factors that were either unbalanced or individually predictive of survival in the two groups (P = 0.70). Pneumonia developed in 59 patients (13 percent) in the intensive care unit within 30 days of enrollment in the study (33 in the placebo group and 26 in the treatment group, P = 0.42). Pneumonia acquired in the intensive care unit and due to gram-negative bacilli was less frequent (P = 0.01) in the treatment group than in the placebo group. The total charges for antibiotics were 2.2 times higher in the treatment group. CONCLUSIONS: Selective decontamination of the digestive tract does not improve survival among patients receiving mechanical ventilation in the intensive care unit, although it substantially increases the cost of their care.

Administration, Topical↗
PubMed1991

Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding.

The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established. Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate [KR], defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding [PB], and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escherichia coli endocarditis. Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta-lactams. For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection. Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams. Univariate regression analysis showed that KR was the major determinant of MED. A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not. The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01). We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD. In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD.

Animals↗
PubMed1991

Ocular kinetics of pefloxacin after intramuscular administration in albino and pigmented rabbits.

We determined the ocular kinetics of pefloxacin, a new fluoroquinolone, when administered by the intramuscular route to albino and pigmented rabbits. In serum of albino rabbits, the area under the concentration-time curve (AUC) for the experimental period was 31.4 +/- 1.07 micrograms.h/ml (mean +/- standard deviation); the AUCs in the aqueous and vitreous humors were high (10.5 +/- 1.90 and 12.4 +/- 3.79 micrograms.h/ml, respectively). Pefloxacin was found in the avascular ocular tissues (30.15 +/- 3.79 micrograms.h/ml in the cornea and 6.98 +/- 1.06 micrograms.h/ml in the lens). In the vascularized tissues, the penetration ratio, defined as tissue AUC/serum AUC, was more than 1. The good intraocular diffusion of pefloxacin might be related to its low molecular weight and to its strong lipophilicity and could explain its clinical efficacy in the treatment of endophthalmitis. In pigmented rabbits, pefloxacin levels were high in the iris (1525 +/- 328 micrograms.h/ml, versus 40.2 +/- 5.08 micrograms.h/ml in albino rabbits) and chorioretina (2600 +/- 422 micrograms.h/ml, versus 48.3 +/- 7.52 micrograms.h/ml in albino rabbits), suggesting that it binds to the pigmentary apparatus.

Animals↗
PubMed1991

[Which compressor should be used to deliver pentamidine aerosols with the Respirgard II?].

Prophylaxis against pneumonia due to Pneumocystis carinii is most often carried out using pentamidine administered as an aerosol. For reasons both of comfort and cost this technique should be developed at home or at least in an extra-hospital environment. Using the Respirgard II as the nebuliser of reference this requires a compressor. We have assessed four different compressors and compared these to pressurised oxygen used in a hospital environment. During the course of nebulisation with a pentamidine aerosol two physical factors may coincide to limit their efficacy. First the deposition of some of the particles on the walls of the apparatus and secondly the production of a particle size which is incompatible with alveolar deposition. This study showed that according to the source of compressed air: 1) the fraction of the pentamidine solution found in an aerosol at the mouthpiece varies from 29 to 62%; 2) the fraction of the aerosol whose particle size is suitable for alveolar deposition (1 to 3 microns) varies from 35 to 48%. The product of these two fractions enables an assessment of the efficiency of each apparatus: 14 to 24% of the pentamidine solution may be deposited at the alveolar level. In addition to this efficiency the duration of the session (from 25 to 50 minutes) for each machine should be taken into consideration when considering the choice of the compressor to be coupled with the Respirgard II in order to improve the comfort and therefore the compliance to the treatment.

Aerosols↗
PubMed1988

Disposition of amopyroquin in rats and rabbits and in vitro activity against Plasmodium falciparum.

The disposition of amopyroquin was studied in rats after a single 50-mg/kg (body weight) oral dose of amopyroquin base. After a rapid absorption phase, the drug concentrations decreased in the plasma, with a terminal half-life of 14.5 h. The drug was widely distributed in the liver and lungs and, to a lesser extent, in the kidneys and spleen. In rabbits, the kinetic parameters were compared after a single 10-mg/kg dose of amopyroquin base through intravenous, intramuscular (i.m.), and oral routes. The similar bioavailability values (0.67 and 0.69) suggested that the drug could be used through i.m. or oral administration. Clearance and distribution volume did not differ significantly among the three modes of administration, and the terminal half-lives were 18.1 +/- 3.3, 23.9 +/- 6.7, and 25.7 +/- 5.4 h for intravenous, i.m., and oral routes, respectively. The ratio of concentrations in erythrocytes and plasma was about 5 in rats and rabbits. Three metabolites were detected in both animal species (one was tentatively identified as the primary amine derivative). The amopyroquin in vitro activity was tested against four chloroquine-susceptible and 11 chloroquine-resistant African Plasmodium falciparum strains. For all isolates, the 50% inhibitory concentrations of amopyroquin were much lower than those of chloroquine and monodesethylamodiaquine.

Absorption↗
PubMed1987

Disposition of monodesethylamodiaquine after a single oral dose of amodiaquine and three regimens for prophylaxis against Plasmodium falciparum malaria.

The disposition of monodesethylamodiaquine was studied in four healthy subjects after a single oral dose of 10 mg/kg amodiaquine base. Amodiaquine was not found in any sample, but the major metabolite monodesethylamodiaquine was detected and was assumed to be the sole derivative that contributed significantly to antimalarial activity in the blood. The best fit for the decay of the metabolite was obtained with a three-compartment model. The half-lives of the first two phases were 3.2 to 11.4 h for t1/2 alpha 1 and 22.7 to 50.3 h for t1/2 alpha 2 in plasma. The half-life of the terminal phase (t1/2 beta) was between 9 and 18.2 days. The concentration in whole blood was 4- to 6-times higher than in plasma. Three schedules (alternate days, weekly, daily) of the conventional prophylactic dose of 10 mg/kg per week were compared in six other healthy subjects. There were significant differences in the plasma monodesethylamodiaquine levels between the three schedules.

Adult↗
PubMed1985

Renal disposition of gentamicin, dibekacin, tobramycin, netilmicin, and amikacin in humans.

The tubular disposition of five aminoglycosides was studied in humans to establish a possible relationship between tubular reabsorption and the nephrotoxicity that has been described in the literature. Thirty-three healthy male volunteers received a continuous intravenous infusion of isotonic saline with inulin, followed 1 h later by inulin plus gentamicin, dibekacin, tobramycin, netilmicin, or amikacin (1 mg/kg per h) or amikacin (4 mg/kg per h) over a period of 2 h. Brain-stem-evoked response audiometry was performed both before and at the end of each infusion. The latency of wave V remained constant whichever antibiotic was considered. The glomerular filtration rate did not vary significantly during the infusion of each drug. The percent fractional excretion was 79 +/- 6, 81 +/- 22, 85 +/- 5, and 99 +/- 9 for gentamicin, dibekacin, tobramycin, and netilmicin, respectively, and 83 +/- 4 and 124 +/- 13 for amikacin at concentrations of 1 and 4 mg/kg per h, respectively. Net balance and renal clearance were similar for the five aminoglycosides when administered at a rate of 1 mg/kg per h. With gentamicin only, fractional excretion was correlated with the urinary flow rate. We can conclude that (i) gentamicin, generally considered the most nephrotoxic agent, had the highest degree of net reabsorption; (ii) netilmicin exhibited a net zero tubular balance; (iii) amikacin had different patterns of tubular disposition according to the dose, i.e., reabsorption at 1 mg/kg per h and secretion at 4 mg/kg per h, raising the hypothesis of a saturable process of reabsorption; and (iv) these differences in tubular reabsorption could account at least in part for the known different nephrotoxic potentials of these five aminoglycosides in humans.

Adult↗
PubMed1985

[Pharmacokinetics of amodiaquine and prevention of Plasmodium falciparum malaria].

Amodiaquine might appear as an alternative in prophylaxis of chloroquine-resistant P. falciparum malaria. In an attempt to explain the discrepancy between its in vivo-in vitro activity, a pharmacokinetic study was conducted in healthy subjects with HPLC assays. The results showed that: amodiaquine was no more detected in the blood, a main metabolite (monodesethyl derivative) appeared as the active form of the drug in vivo, metabolite's half-life had a mean value of 15.6 +/- 5.4 days. This study shows that monodesethylamodiaquine (and not amodiaquine) must be monitored in vitro. Furthermore the high individual variations of blood levels and half-life's values suggest that the weekly prophylactic schedule must be eventually re-evaluated.

Adult↗
PubMed1984

Vancomycin pharmacokinetics in critically ill patients.

Peak and trough vancomycin serum levels were measured in 37 severely ill patients following dosing using the Moellering nomogram. The peak and trough serum concentrations were 61.2 +/- 23 and 22.6 +/- 16.5 mg/l, respectively, and higher than expected. Vancomycin pharmacokinetics obtained from 10 other patients were also studied. In five patients with a creatinine clearance greater than 1 ml min-1 kg-1, a mean plasma elimination half-life of 7.8 +/- 2.8 h was calculated. In the five other patients with markedly reduced renal function (creatinine clearance less than or equal to 1 ml min-1 kg-1), the mean elimination half-life was 18.3 +/- 10.2 h. A correlation was observed between the vancomycin and creatinine clearance. Important inter-patient variations of vancomycin clearance for the same creatinine clearance was also noted. Tubular damage in critically ill patients with severe sepsis may explain our results of the decreased vancomycin elimination.

Creatinine↗
PubMed1982

[Sensitivity to mezlocillin Gram-negative aerobic bacilli according to their pattern of resistance to the usual beta-lactam antibiotics (author's transl)].

Gram-negative aerobic bacilli (Enterobacteria, Pseudomonas, Acinetobacter) isolated in clinical circumstances at the microbiology of the Claude Bernard Hospital, Paris, are classified according to their resistance to the usual beta-lactam antibiotics routinely tested: ampicillin, carbenicillin, cefalotin. The MICs of mezlocillin were measured on 204 strains and compared to the results obtained with older drugs in each group.

Acinetobacter↗
PubMedDate not supplied

Nebulized cyclosporine for prevention of acute pulmonary allograft rejection in the rat: pharmacokinetic and histologic study.

BACKGROUND: With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration. METHODS: In a pharmacokinetic study, the cyclosporine A was given either by intramuscular injection (10 mg/kg) or by aerosol at 10 and 25 mg/kg doses; 70 rats were killed at 25 and 50 minutes and 2, 4, 6, 8, 12, 24, or 48 hours after cyclosporine A administration. Cyclosporine A levels were measured in whole blood and in the lung. The areas under the concentration time curves were determined. Twenty-four lung transplantations were then performed. The rats were killed on postoperative day 9. Acute rejection was scored on a scale of 0 to 4, and cyclosporine A trough levels were measured in the lung and in the blood. RESULTS: With a jet nebulizer, the mass median aerodynamic diameter was 2.5 microns, with a standard geometric deviation of 2.3. In blood, the area under the concentration curve was greater for intramuscular (80.6 ng.hr/ml) than for aerosol administrations at 10 (15.1 ng.hr/ml) and 25 mg/kg (41.0 ng.hr/ml) doses. In the lungs, the area under the concentration curve was greater for the aerosol route at 25 mg/kg doses (588 ng.hr/mg) than for the low-dose (200 ng.hr/mg) or intramuscular administration (200 ng.hr/mg). The lung targeting index of cyclosporine A (ratio area under the concentration curve-lungs/area under the concentration curve-blood) was greater for both aerosol administrations than for the intramuscular route. In the study of the prevention of acute rejection, rats without immunosuppression (n = 6), rats receiving daily doses of cyclosporine A intramuscularly (10 mg/kg), and rats with aerosolized cyclosporine A daily (10 and 25 mg/kg/day) showed mean grades of acute rejection of, respectively, 4, 2.03 +/- 0.27, 2.33 +/- 0.52, and 2.17 +/- 0.46. The deposition of nebulized cyclosporine A was lower in transplanted than in native lung. CONCLUSIONS: Nebulized cyclosporine A allows better pulmonary concentration than intramuscular administration, and results in lower systemic levels. Prevention of acute rejection is as good with aerosolized cyclosporine A as with intramuscular cyclosporine A. This first pharmacokinetic study of nebulized cyclosporine A could lead to clinical applications.

Administration, Inhalation↗