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Biomedical subjects

J M Brogard

Publications and source records attributed to J M Brogard.

At least 109 records · Page 6Linked to original sources
PubMed1982

Ototoxicity of tobramycin in humans - influence of renal impairment.

The effects of prolonged tobramycin administration (given in repeated injections over a 15-day period) on auditory and vestibular functions were studied in normal subjects, in patients with renal impairment, and in chronic nephritic patients undergoing hemodialysis. With the doses used in this study, the repeated administration of tobramycin resulted in blood accumulation only in the group of patients with renal impairment. In one single case, administration of tobramycin was followed by a transient aggravation of a pre-existing renal impairment. Cochlear and vestibular functions were evaluated before treatment and repeated during and after drug administration. In normal subjects, a dosage of 50 mg/8 h failed to produce cochlear and vestibular dysfunction; but with dosages of 75 mg/8 h and 100 mg/8 h, changes in vestibular reflectivity occurred frequently, mostly of the irritative type. Generally moderate, but quite often slight changes persisted (5 of 10 cases). They were not accompanied by auditory or vestibular clinical signs. In patients with impaired renal function and in those undergoing chronic hemodialysis, vestibular impairment is customary and most often of the deficiency type. Half of the cases still showed detectable changes on follow-up evaluation that was performed 10 days after discontinuation of the drug.

Anti-Bacterial Agents↗
PubMed1982

Pharmacokinetic profile of benoxaprofen in subjects with normal and impaired renal function, prediction of multiple-dose kinetics.

The pharmacokinetic profile of benoxaprofen given as a single oral dose of 600 mg was determined comparatively in 5 healthy volunteers and in 15 patients with various degrees of renal insufficiency (5 of whom were undergoing maintenance hemodialysis). In normal subjects, the half-absorption period (Ka) was 0.63 hours. A mean maximum concentration of 47.3 micrograms/ml could be predicted at 3.6 hours after the dose intake. Serum level decrease was particularly slow. The overall elimination rate constant, Ke, was 0.0234(h-1) and biologic half-life amounted to 28.8 hours. Values for total clearance (Ct=4.8 ml/min/1.73 m2) and renal clearance (Cr=1.6 ml/min/1.73 m2) were low. Of the administered dose of benoxaprofen, 13.9% was recovered in the urine over a 24-hour period. Renal insufficiency did not induce major changes in pharmacokinetic parameters. Under such conditions, it seems advisable to reduce the dose to one-half only in patients with a creatinine clearance of less than 10-20 ml/min/1.73 m2. Predicted serum levels theoretically achieved after repeated administration of a 600-mg dose of benoxaprofen every 6, 12, 24, 36 and 48 hours were calculated. From this evaluation, it appears that therapeutically effective and adequate levels could be obtained after administration of a 600-mg dose every 12 ot 24 hours.

Adult↗
PubMed1981

[Juvenile diabetes of recent onset. Sustained insulin remission by means of preprogrammed insulin infusion (author's transl)].

Seven young insulin-dependent diabetic patients were treated within 45 days at the latest from the onset of the disease by programmed insulin infusions delivered with an insulin pump. In every case normal serum glucose levels were obtained. At the end of each 84-hour infusion, an attempt was made to institute oral antidiabetic treatment. This was successful in 6 patients after 2 or 3 infusions and in one patient after 3 infusions followed by 2 months' conventional insulin therapy and a 4th infusion. In 5 patients (71%), oral treatment could be continued for more than 3 months, which indicates sustained remission of insulin-dependence. These results are comparable to those achieved with an artificial pancreas and can be explained by optimal diabetes control during the programmed infusions. The method has the advantages of being simple and relatively inexpensive.

Administration, Oral↗
PubMed1981

[Benoxaprofene: pharmacokinetic profile in the normal subject and patients with renal insufficiency; evaluation of anticipated serum levels].

The pharmacokinetic profile of benoxaprofene, administered in a single oral dose of 600 mg, has been determined comparatively in 5 normal subjects and 15 patients with renal insufficiency (five of whom were on chronic hemodialysis). In the normal subject, the half-absorption time (Ka) was 0.63 hours; a mean theoretical maximal concentration of 47.3 micrograms/ml was reached 3.6 hours after administration of the drug. The decrease in serum levels was particularly slow, the coefficient of total elimination (Ke) being 0.0241(h-1) and the biological half-life attaining 28.8 hours. :The total clearance (Ct = 4.8 ml/min/1.73 m2) and renal clearance (Cr =1.6 ml/min/1.73 m2) values were low. 13.9% of the ingested dose of benoxaprofene was recovered in the 24 hours urinary volume. Renal insufficiency does not significantly change the pharmacokinetic parameters. It appears advisable to reduce the dosage by half only in patients with a Cr clearance of less than 10-20 ml/min/1.73 m2. The theoretical serum values reached after administration of 600 mg benoxaprofene repeated every 6-12-24-36 or 48 hours have been calculated and it has been found that effective concentrations can be obtained by administration of 600 mg every 12 or 24 hours.

Administration, Oral↗
PubMed1981

Biliary excretion of cefuroxime. Experimental and human study.

The biliary excretion of cefuroxime was studied experimentally, using a preparation of isolated rabbit liver (n = 5) perfused in vitro during 3 h; 0.92% of the cefuroxime (10 mg) added to the circulating blood was found in the bile, while peak antibiotic activity reached a mean value of 8.0 +/- 1.1 microgram/ml. In man, 1 h after a single intravenous injection of cefuroxime (0.5 g), a maximum concentration of 4.0 +/- 1.6 microgram/ml was found in the duodenal aspiration fluid collected from 5 healthy subjects. In 10 patients with T-tube drainage, a mean biliary peak of 10.3 +/- 2.4 microgram/ml was observed 2 h after intravenous injection of the same dose; the biliary excretion of cefuroxime during the 12-hour experiment corresponded to 0.13% of the administered dose. Assays performed during cholecystectomy in 10 patients 1 h after cefuroxime intravenous injection of 0.5 g showed concentrations of 11.9 +/- 0.8 microgram/ml in the serum, 12.0 +/- 1.5 microgram/ml in the common duct bile and 7.4 +/- 1.1 microgram/ml in the gallbladder bile. These results were compared with those observed after administration of 11 other beta-lactam antibiotics in identical experimental and clinical conditions.

Animals↗
PubMed1981

[Experimental and clinical study of the biliary elimination of mezlocillin (author's transl)].

The biliary elimination of mezlocillin was studied in 5 perfused rabbit liver preparations. After adding 10 mg of mezlocillin to the perfusion medium, the biliary peak averaged 758 +/- 129 microgram/ml and total mezlocillin recovery within 3hr amounted to 20.3% of the administered dose. In 5 healthy subjects, the mean levels in the duodenal fluid collected during the 4 hrs following an infusion of 5 g of mezlocillin ranged from 440 to 637 microgram/ml. In cholecystectomized patients provided with a T-tube drainage, the maximal concentration after the same dosage (n = 10) was 505 +/- 158 microgram/ml and cumulative biliary excretion of mezlocillin over a 12 hr period corresponded to 1.3% of the administered dose. Under the same conditions, after intra-muscular injection of 1 g of mezlocillin to 10 subjects, the biliary peak averaged 292 +/- 58 microgram/ml and the total biliary recovery 2.6% of the administered dose. In 10 patients undergoing biliary tract surgery, the levels determined 1 hr after IV injection of 2 g of mezlocillin reached 896 +/- 196 microgram/ml and 402 +/- 133 microgram/ml in the main duct and in the gallbladder bile, respectively. These results were compared with the values obtained under identical conditions with 12 other beta-lactam antibiotics.

Animals↗
PubMed1981

[Experimental and clinical study of the biliary excretion of cefamandole (author's transl)].

Using the isolated rabbit liver perfusion model, it could be shown that 11.1% of 10 mg of cefamandole added to the circulating blood were recovered in the 3 hours collected bile. The maximal biliary antibiotic activity averaged 214 +/- 37 microgram/ml. In humans a peak concentration of 19.0 +/- 6.1 microgram/ml could be measured in the aspirated duodenal fluid (n = 5) 1 hour after a single intravenous injection of 1 g of cefamandole. In 10 patients provided with a Kehr's drainage, a mean biliary peak of 141.4 +/- 86.4 microgram/ml was observed at the 2nd hour after administration of the same dose of cefamandole. Assays performed during cholecystectomy showed 1 after the intravenous injection of 1 g of cefamandole mean values of 64.0 +/- 18.0 microgram/ml in the gallbladder bile and 87.2 +/- 16.1 microgram/ml in the common duct bile. These data are compared with those obtained by administration of 11 other beta-lactamines under similar experimental and clinical conditions.

Animals↗
PubMed1980

Biliary elimination of mezlocillin: an experimental and clinical study.

The biliary elimination of mezlocillin, a new semisynthetic penicillin of the acyl-ureido-penicillin group, was investigated in vitro in rabbit liver preparations and in vivo in humans. Experimentally, mezlocillin recovery in the bile during perfusion of isolted rabbit liver (3 h; n = 5) averaged 20.3% of the administrered dose (10 mg). The mean peak concentration in the bile (758 +/- 129.3 micrograms/ml) was reached between 0.5 and 1 h. Biliary clearance was 169 ml/h. In healthy subjects (n = 5), the concentrations of antibiotic measured in the duodenal fluid during a period of 4 h after intravenous administration of 5 g of mezlocillin ranged between 440 and 637 micrograms/ml. In 10 cholecystectomized patients provided with a T-tube, intramuscular injection of 1 g of mezlocillin resulted in a biliary peak concentration of 295.7 +/- 58.1 micrograms/ml. Mean total amount of antibiotic eliminated in the bile over 12 h corresponded to 2.6% of the administered dose. Assays performed during surgery after intravenous administration of 2 g of mezlocillin (n = 10) showed antibiotic activity of 895 +/- 196 micrograms/ml in the common duct bile and 402 +/- 133 micrograms/ml in the gallbladder bile. These data were compared with the values determined for 11 other beta-lactamines studied under identical conditions.

Animals↗
PubMed1980

[Variations of the coefficient of glucose assimilation in normal pregnancy].

Three hundred eleven intravenous glucose tolerance tests were performed in normal pregnant women between the 8th and the 40th week, and compared with similar tests performed in two groups of non-pregnant women, one group on oral contraceptives, the other not. There was a relative improvement in glucose tolerance at the beginning of pregnancy followed by marked loss of tolerance after the 24th week. This evolution is due to the physiologic adaptation of the maternal pancreas to fetal and placental metabolism. The range of normality for the glucose disappearance rate differs before and after the 24th week of pregnancy, and this must be recognised in setting diagnostic criteria for gestational diabetes. Consideration of simultaneous studies of glucose tolerance and insulin secretion at various periods of pregnancy suggests that changes in K value are more closely correlated with variations in peripheral insulin effects than with changes in insulin secretory function of the maternal pancreas.

Female↗
PubMed1979

[The oral glucose tolerance test during normal pregnancy (author's transl)].

Physiological changes in carbohydrate tolerance were studied between the beginning and end of pregnancy. Amongst 145 oral glucose tolerance tests performed between the 9th and 40th weeks, results indicated that carbohydrate tolerance evolved throughout pregnancy. The first 24 weeks were characterised by a change in the shape of the glucose tolerance curve, in the form of horizontalisation of the terminal part, but with no increase in early blood glucose figures. It was only after the 24th week that mean blood glucose levels were seen to be increased. The interpretation of glucose tolerance tests during pregnancy should take these physiological changes into account. Critical values, above which diabetes must be suspected, are different at the beginning and end of pregnancy. The critical point would appear to be around the 24th week.

Adult↗
PubMed1979

Cefamandole pharmacokinetics and dosage adjustments in relation to renal function.

The pharmacokinetic characteristics of cefamandole were determined after intravenous administration of a 1-Gm dose to 10 subjects with normal renal function, 10 patients with stabilized renal failure, and five chronic nephritic patients included in a intermittent hemodialysis program. In normal subjects, biological half-life (t1/2) averaged 0.94 hour, the overall elimination rate constant (Ke) was 0.7378 (hr-1), total clearance (Ct) was 223 ml/min/1.73 m2, renal clearance (Cr) was 164 ml/min/1.73 m2, and urine recovery of cefamandole over the 6 hours following a dose amounted to 74 per cent of the administered dose. In patients with stabilized renal failure and in patients on hemodialysis, biological half-life was markedly increased, with a theoretical value of 10.4 hours in case of a creatinine clearance of zero. The amount of antibiotic extracted over a 6-hour dialysis period accounted for 29 per cent of the cefamandole present in the vascular compartment at the beginning of the dialysis procedure. A significant correlation was established between the values of Ke and creatinine clearances, Ccr: Ke = 0.0289 + 0.0063Ccr (r = 0.937). This relationship was used to calculate the loading dose (LD), maintenance doses (D), and dosage intervals (tau) with regard to renal function. From these data recommendations regarding the adjustment of cefamandole dosage to the renal status can be made.

Cefamandole↗
PubMed1979

Evaluation of the biliary excretion of pencillin G.

Biliary excretion of penicillin G was studied experimentally by perfusion of isolated rabbit liver. Under these conditions, bile recovery accounted for 5% of the amount of penicillin G added to the perfusing blood (10 mg). In man, after intravenous administration of a 599-mg dose of penicillin G (1,000,000 U) to patients provided with T-tube drainage (n = 10), the maximum biliary level averaged 18.0 +/- 8.0 microgram/ml at 2 h; biliary recovery of penicillin G accounted for 0.12% of the administered dose. The excretion of penicillin G in the juice collected through duodenal tubing in normal subjects averaged 0.07% of the administered dose. Peroperative assays showed that the concentrations determined 1 h after intravenous administration 599 mg of the drug attained 45.7 +/- 16.7 microgram/ml in the gallbladder bile and 93.5 +/- 16.3 microgram/ml in the common-duct bile.

Animals↗
PubMed1979

[Evaluation of the biliary excretion of penicillin G. (author's transl)].

Biliary excretion of penicillin G was studied experimentally by perfusion of isolated rabbit liver. Under these conditions, bile recovery accounted for 5% of the amount of penicillin G added to the perfusing blood (10 mg); peak biliary level averaged 135.3 micrograms/ml. In man after intravenous administration of a 599 mg dose of penicillin G (1 MU) to patients provided with T-tube drainage (n = 10), the maximum biliary concentration averaged 18.0 +/- 8.0 micrograms/ml at 2 hours; biliary recovery of penicillin G accounts for 0.12% of the administered dose. The excretion of penicillin G in the juice collected through duodenal tubing in normal subjects averaged 0.07% of the administered dose (599 mg IV). Per-operative assays showed that the concentration determined at 1 hour after intravenous administration of the drug (599 mg) in the gallbladder bile (45.7 +/- 16.7 micrograms/ml) and common duct bile (93.5 +/- 16.3 micrograms/ml) were definitely higher (4.5--9 times) than the serum levels measured simultaneously. The biliary excretion of penicillin G is compared with the biliary elimination of a certain number of beta-lactam derivatives studied under the same conditions (ampicillin, metampicillin, carbenicillin, cefalothin, cefaloridine, cefacetrile, cefalexin, cefazolin).

Animals↗
PubMed1979

[Screening for diabetes during pregnancy (author's transl)].

Screening for diabetes, or more commonly the study of maternal glucose tolerance, a routine procedure during pregnancy. The first step consists of assessing the diabetic risk for the patient. Screening tests should be applied early if risk factors for diabetes are present, and/or at a later stage in all pregnant women. The initial test should always be provoked hyperglycemia by the intravenous route. According to the value of the glucose assimilation coefficient K, the test will be repeated using the oral route. Screening can only be effective if applied to all pregnant women.

Administration, Oral↗