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Biomedical subjects

A Leroy

Publications and source records attributed to A Leroy.

At least 73 records · Page 4Linked to original sources

[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↗

Characterization of a monoclonal antibody that binds to apolipoprotein E and to lipoprotein of human plasma containing apo E. Applications to ELISA quantification of plasma apo E.

This study describes the development of an enzyme-linked immunosorbent assay for human apolipoprotein E (apo E). A mouse monoclonal IgG1 antibody named E01 against apolipoprotein E was selected from five antibodies secreted by hybridomas. This antibody had a high affinity for apo E [K = 1.2 x 10(7) L.M-1 for purified apo E and K = 1.05 x 10(7) L.M-1 for native apo E in very low density lipoproteins) in liquid phase and recognized every isoform of apo E but not other proteins in VLDL. Competition experiments with 125I apo E showed that its binding affinity for the E in every density class (VLDL, HDL, LDL) and in serum was the same. This antibody was used for the quantification of human apo E in serum by enzyme linked immunoassay. E01 was coated on microtiter plates and a polyclonal peroxidase-conjugate was used as second antibody. A good correlation was observed between the values obtained for apo E using both monoclonal and polyclonal antibodies.

Animals↗

Comparative pharmacokinetics of tromethamine fosfomycin and calcium fosfomycin in young and elderly adults.

The pharmacokinetics of two oral forms of fosfomycin, tromethamine (trometamol) salt and calcium salt, were studied in five young (age, 29 +/- 3 [standard deviation] years) and eight elderly (age, 72 +/- 6 years) adults. The subjects received a single 40-mg/kg (body weight) (approximately equal to 3-g) calcium fosfomycin dose and a 25-mg/kg (approximately equal to 2-g) tromethamine fosfomycin dose in fosfomycin acid form. Blood and urine samples were collected for 24 h. Antibiotic concentrations in serum and urine were measured by microbiological assay. In all subjects, the peak levels of the calcium salt in serum were two- to fourfold lower than those of the tromethamine salt (6 to 7 and 18 to 22 micrograms/ml, respectively), indicating poor intestinal absorption of the calcium form. The elimination half-life of the two oral forms was about 5 h in young adults, and the half-life was only moderately longer in elderly subjects, with large individual variations: 8.28 +/- 5.51 h for tromethamine fosfomycin and 11.80 +/- 6.86 h for calcium fosfomycin. In elderly subjects, absorption of the tromethamine salt form was not modified, but the time to peak level was delayed for the calcium salt (2.58 +/- 0.54 h versus 1.41 +/- 0.67 h in young adults). Pharmacokinetic elimination of the two forms of fosfomycin was only moderately affected in elderly subjects; we observed lower urinary elimination, about 58 versus 28% of the dose in 24-h urines for the tromethamine salt and decreased renal clearance of both forms. However, the dosages of tromethamine and calcium fosfomycin need not be adjusted for elderly subjects who have endogenous creatinine clearances above 50 ml/min per 1.73 m2.

Adult↗

[Pharmacokinetics of trometamol-fosfomycin in patients with renal insufficiency].

Trometamol fosfomycin is a new form of fosfomycin used orally. We have studied pharmacokinetics of this antibiotic in 23 uraemic patients with various degrees of renal insufficiency. The control group was 5 young adult males with a creatinine clearance of 127 +/- 20 ml/mn. All subjects received a single oral dose of 25 mg/kg trometamol fosfomycin. Serum and urine concentrations of fosfomycin were assayed by a microbiological method. Cmax, tmax, AUC were significantly higher in uraemic patients than in normal subjects. t 1/2 beta were prolonged in uraemic patients. Thus it is necessary to modify usual dose regimen when creatinine clearance is below 50 ml/mn.

Administration, Oral↗

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↗

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↗

Standardization of an enzymometric assay for apolipoprotein A-I by using mixtures of monoclonal antibodies).

For the standardization of human plasma apolipoprotein A-I assay two well characterized monoclonal antibody mixtures were used to develop a sandwich immunoenzymometric assay. The monoclonal antibody mixture 1 (A05-A17-A30) in solid phase technique was selected on the basis of its higher binding capacity of [125I]HDL (41 ng per well) compared to polyclonal antibody (23 ng per well). The epitopes recognized by monoclonal antibody mixture 1 are surface antigenic sites of apolipoprotein A-I expressed on native HDL as determined by competitive inhibition of labeled HDL. The peroxidase conjugated monoclonal antibody mixture 2 (A03-A05-A17-A51) was selected on the basis of its ability to bind to apolipoprotein A-I captured by monoclonal antibody mixture 1. For this, we used the 125I-labeled monoclonal antibodies. Under optimized assay conditions, the immunoenzymometric assay is precise (intra- and inter-assay coefficients of variations 5.4% and 9.2% respectively). It yields plasma apolipoprotein A-I values that correlate highly with those obtained with polyclonal antibody (r = 0.96). So the use of well characterized monoclonal antibody mixtures reacting only to surface antigenic sites of apolipoprotein A-I present on native lipoprotein may provide the possibility of standardization of apolipoprotein A-I measurement.

Antibodies, Monoclonal↗

[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↗

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↗