Biomedical subjects
J M Brogard
Publications and source records attributed to J M Brogard.
[Essential labile diabetes (author's transl)].
"Essential labile diabetes" is an insulin-dependent diabetes, in the course of which irregular and unpredictable hyperglycemias, frequently with ketosis, and sometimes serious hypoglycemias alternate. In spite of careful treatment with insulin, diet and suitable hygienic measures, this form of diabetes cannot be influenced. Fortunately, it seldom occurs, not more frequently than in 1 to 2% of diabetics. Various attempts have been made to explain the pathogenesis of this form of the disease. The most probable explanation is that there is an almost complete exhaustion of insulin secretion. This hypothesis is based on the extremely low level of the C peptide below 0.60 ng/ml, whereas in non-labile insulin-dependent diabetics the C peptide amounts to more than 2.2 ng/ml
Biliary excretion of ampicillin: experimental and clinical study.
The biliary excretion of ampicillin was studied in various conditions. Using an isolated perfused rabbit liver preparation, 4.1% of the amount of ampicillin added to the circulating blood (10 mg) was recovered in the bile where the maximum antibiotic activity (mean: 104 +/- microng/ml) was 4 times higher than in the serum (mean: 24.1 +/- 3.4 microng/ml). In man, provided with T-tube drain, the oral or intravenous administration of 500 mg ampicillin resulted in a biliary excretion of 0.10% of the administered dose. The biliary concentrations thus obtained equalled or exceeded for several hours the minimal inhibitory concentration of the organisms included in the antibacterila spectrum of ampicillin justifying thus the use of this antibiotic in the treatment of biliary tract infections. Per-operatory assays showed that in patients with gallbladder disease or with cystic duct obstruction, ampicillin levels in the gallbladder bile were markedly lower than in the common duct bile.
Pharmacokinetics of cefazolin in patients with renal failure; special reference to hemodialysis.
The pharmacokinetic constants of cefazolin were determined comparatively in ten normal subjects, 12 patients with renal failure, and ten patients on repeated hemodialysis. Significant correlations could be established between the creatinine clearance values and the overall elimination rate constants (Ke), serum half-lives (T 1/2), plasmatic areas (Ftot), urinary recoveries (uo-6 hr), and renal clearances of the antibiotic (Cr). The pharmacokinetic changes produced by extrarenal removal were also studied. On the basis of the obtained results, a dosage schedule adjusted to renal status was proposed.
[Biliary transport, bile levels and entero-hepatic cycle of antibiotics. Personal study of the biliary elimination of beta-lactamines].
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Biliary excretion of ampicillin, metampicillin and carbenicillin.
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Experimental and clinical pharmacology of metampicillin in the biliary tract.
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Adjustment of cephaloridine (Keflodin): dosage according to its pharmacokinetics.
The determination of the serum and urine concentrations of cephaloridine permitted calculation of the pharmacokinetic constants of this antibiotic: after administration of a 1-gram intravenous dose in five normal subjects; after administration of a 1-gram intramuscular dose in five normal subjects, five patients with renal impairment and five patients on maintenance hemodialysis. In normal subjects, serum half-life averaged 1.56 h (Ke=0.4445) after intravenous administration and 1.63 h (Ke=0.4254) after intramuscular administration of a 1-gram dose of the antibiotic. The urinary excretion of cephaloridine over the 6 h following its intramuscular administration in normal subjects amounted to 56.4% of the administered dose. The renal clearance of cephaloridine was 194 ml/min. A linear correlation (Ke=0.0670+0.0028 CrCl) was established between overall elimination rate-constant values and the creatinine clearances of the patients under investigation. These data were used to calculate the maintenance and loading doses and intervals adjusted to creatinine clearance values. Accurate dosage regimens adjusted to the renal status of each individual patient were derived from the calculated values.
[Biliary elimination of metampicillin. Experimental and clinical study (author's transl)].
Under the conditions of the isolated rabbit liver perfusion, metampicillin was found to be excreted at a high rate in the biliary tract : bile contains 46,5% of the administered dose. Hepatic uptake of metampicillin seems to be early and marked. In man, the biliary elimination of this antibiotic varies according to the route of administration. Only moderate biliary levels of metampicillin were obtained after oral administration ; on the contrary, extremly high biliary concentrations were found when antibiotic was injected intravenously. When parenteraly administered, metampicillin appears to be a particularly suitable penicillin for the treatment of biliary tract infections.
Cephacetrile--application of pharmacokinetic data to dosage determination.
This pharmacokinetic investigation was based on the determination of serum and urinary levles of cephacetrile in 50 subjects given single intramuscular or intravenous doses of 0.5 or 1 gm of the antibiotic; 30 normal subjects, 10 patients with renal insufficiency, and 10 patients with chronic nephritis undergoing maintenance haemodialysis were included in this study. In normal subjects, mean serum half-life was 1.09 hours (Ke = 0.6337) after intramuscular injection of 0.5 gm cephacetrile, 1.31 hours (Ke = 0.5276) after intramuscular injection of 1 gm, and 0.89 hours (Ke = 0.7806) after intravenous injection of 1 gm. Absorption half-life was 0.45 hours after intramuscular injection of 1 gm cephacetrile. The urinary elimination of cephacetrile over the first 6 hours after injection was on the average 72.7% of the administered dose. After intravenous injection of 1 gm of the antibiotic, the plasma clearance of cephacetrile was 407 ml/min., and its renal clearance 313 ml/min. A linear correlation was found between the values of overall elimination rate constant (Ke) and creatinine clearance in the subjects under investigation (Ke = 0.0080 + 0.0061 ClCr). The established pharmacokinetic characteristics were used to calculate the maintenance and loading doses as well as the intervals between injections adjusted to creatinine clearance. These data constitute true dosage schemes adapted to the particular case of each patient according to his kidney function.
[Diagnosis of adiastole].
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Determination of cefalexin pharmacokinetics and dosage adjustments in relation to renal function.
Following oral administration of a single 500-mg dose of cefalexin, serum and urine levels of the antibiotic were determined comparatively in ten normal subjects, ten patients with renal impairment, and ten patients with chronic nephritis on maintenance hemodialysis. In normal subjects, mean serum peak levels (12.0 +/- 0.8 mcg/ml) were observed 2 hours after drug administration. Absorption half-time (Ta1/2) averaged 0.82 hour and mean serum half-life (T 1/2) was 1.03 hours. Urinary recovery of cefalexin over a 6-hour period amounted to 64 per cent of the ingested dose. The renal clearance of the drug was 214 ml/min. In patients with renal impairment and in patients on maintenance hemodialysis, total elimination rate constant (Ke) was markedly lower (CrCl=0; Ke=Km=0.0766), whereas serum half-life (T 1/2) was significantly increased, reaching theoretically 8.47 hours in patinets with creatinine clearance of 0 ml/min. A correlation was established between Ke values and the creatinine clearances of the patients under study (Ke=0.0766 + 0.0060 CrCl). Initial loading doses, maintenance doses, and intervals adjusted to creatinine clearances were calculated from these data; accurate dosage schedules well adjusted to the renal status of each individual patient were derived from the calculated values.
Dosage adjustments of cefazolin according to the pharmacokinetics of this new cephalosporin.
Serum and urine levels of cefazolin were studied: 1. following a single 500mg intra-muscular dose of the drug in normal subjects (n = 10), in patients with renal impairment (n = 12) and in patients undergoing maintenance hemodialysis (n = 10); 2. following a single 500 mg intra-venous dose of the drug in normal subjects (n = 10). In normal subjects, serum half-lives averaged 1.75 hour after intravenous injection (Ke = 0.395) and 2.22 hours after intra-muscular injection (Ke = 0.312); urinary recovery of cefazolin over a six hours period amounted to 61% after intra-venous injection and to 47.5% after intra-muscular injection. The renal clearance of the drug approximated 40 ml/mn. A linear correlation (Ke = 0.022 + 0.0028 CrCl) was established between the overall elimination rate-constants and the creatinine clearances in the subjects under investigation. The various pharmacokinetic constants thus obtained can be used to calculate the maintenance doses, loading doses and dosage intervals adjusted according to creatinine clearances. These data actually yield dosage regimes adapted to each individual case according to the degree of renal function.
The biliary excretion of cefazolin.
The biliary excretion of cefazolin was studied by perfusion of isolated rabbit livers. Under these conditions, 6.7 percent of the amount of cefazolin added to the circulating blood was excreted in bile, and concentrations of drug in bile were significantly higher than concentrations in serum. Biliary excretion of cefazolin was also studied in humans after the intravenous administration of 500 mg of the drug. In 10 normal subjects, maximal concentrations of cefazolin (17.10 plus or minus 8.5 mug/ml) in the fluid obtained by duodenal tubing were attained 1-2 hr after administration of cefazolin. Concentrations were similar in bile collected by external drainage from five cholecystectomized patients (maximal levels, 14.0 plus or minus 4.7 mug/ml) 1-2 hr after injection. Assays during cholecystectomy showed that 1 hr after injection, cefazolin levels were much higher in common duct bile (31 plus or minus 11 mug/ml) than in gallbladder bile (5 plus or minus 2 mug/ml).
[Diffusion of cephazolin in the biliary tract].
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[Tobramycin: pharmacology in man].
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[A study of the cochleo-vestibular tolerance of tobramycin in man. Preliminary study].
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[The course of serum levels of a new cephalosporin, cephacetrile, as a function of renal elimination capacity].
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