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Biomedical subjects

J M Brogard

Publications and source records attributed to J M Brogard.

At least 91 records · Page 5Linked to original sources
PubMed1985

[Biliary excretion of apalcillin. Experimental study and evaluation in man].

Biliary excretion of apalcillin, a new derivative of the ureido-penicillin group, was investigated both experimentally and in humans. After adding 10 mg of this antibiotic to the circulating blood of an isolated rabbit liver perfusion model (n = 5), mean total apalcillin biliary recovery (0-3 h) accounted for 30.7% of the administered dose; the biliary peak averaged 686.0 +/- 135.9 micrograms/ml. In 5 healthy subjects, a mean maximum level of 1088 +/- 582 micrograms/ml was measured in the duodenal fluid collected during the 4 hours following an i.v. injection of Ig of apalcillin. In 10 cholecystectomized patients provided with T-tube drainage, after the same dosage, a mean biliary peak of 2093 +/- 859 micrograms/ml was reached at the third hour and cumulative biliary recovery of apalcillin over a period of 12 hours amounted to 12.1% of the injected dose. In 20 patients, undergoing biliary tract surgery, intra-operative assays performed 1 hour after i.v. injection of 1 g of apalcillin, showed simultaneous mean antibiotic activity of 65.5 +/- 5.0 micrograms/ml in serum, 3860 +/- 551 micrograms/ml in main duct bile and 2552 +/- 627 micrograms/ml in gallbladder bile. The results of these investigations were compared with data previously obtained under identical procedures with 13 other beta-lactam derivatives.

Ampicillin↗
PubMed1985

Genetically engineered insulin: five years of experience.

Genetically engineered insulin is the first application of recombinant DNA technology which has gone into industrial production and wide clinical use. Four years after the first clinical trials, it appears that there are only minor pharmacokinetic differences from purified pork insulin; in particular, a faster subcutaneous absorption for both regular and NPH forms. The hypoglycaemic potency of genetically engineered insulin is identical to that of purified pork insulin but a weaker effect on counterregulatory hormones has been reported. However, the main advantage of biosynthetic human insulin is its species specificity, which reduces its immunogenicity. Convincing results were obtained in patients suffering from insulin-produced adverse reactions such as insulin resistance or allergy, although biosynthetic human insulin does have some immunological properties and crossreacts with beef or pork insulin antibodies.

Animals↗
PubMed1984

[Insulin-dependent diabetes with acute onset. Remissions induced by early temporary blood glucose normalization].

Within 6 months of the acute onset of an insulin-dependent diabetes, remission of insulin-dependence was attempted in 30 hospital patients by strict control of glycaemia obtained in a few days with intravenous infusions of insulin, using a macropump. This was followed by an oral antidiabetic treatment, and the patients were considered in remission when metabolic control was achieved. By this method remission of insulin-dependence was obtained in 90% of the patients; it lasted for more than 1 year on average, and its degree seemed to depend on the time elapsed between the clinical onset of the disease and the beginning of the intravenous treatment but also, to a lesser extent, on the residual secretory capacity of the pancreas when this treatment was instituted. Thus, an intensive metabolic control increases the effectiveness of an oral treatment as regards both number of patients improved and duration of remission. When administered alone at the onset of the disease the oral treatment is only effective in about 30% of the cases.

Adolescent↗
PubMed1984

[Biosynthetic human insulin. Pharmacokinetic characteristics and activity in normal subjects].

The pharmacokinetics and pharmacodynamic effects of intravenously injected (0.06 U/kg) human biosynthetic insulin of recombinant DNA origin and purified porcine insulin, both regular, were compared in 10 healthy volunteers. Both had identical immunological properties. Some of their pharmacokinetic features, such as total plasma clearance and bioavailability, were similar, but they appeared to differ in biological half-life, elimination rate constant and apparent volume of distribution. No appreciable difference was found between their hypoglycaemic activity and their inhibitory effect on endogenous insulin secretion. However, hyperglucagonaemia seemed to be less pronounced after human biosynthetic insulin than after purified porcine insulin. These findings are discussed by comparison with the results of other studies on human biosynthetic insulin.

Adult↗
PubMed1984

Biliary elimination of apalcillin in humans.

Apalcillin was administered intravenously as a single 1-g dose on day 8 after surgery to 10 cholecystectomized patients with T-tube drainage. A peak of 2,093 +/- standard error of the mean 859 micrograms/ml of bile was attained at 3 h after dosage. Biliary recovery over a 12-h period amounted to 12.2% of the dose. In 20 patients undergoing biliary surgery, apalcillin concentrations 1 h after a 1-g dose were 65.5 +/- 5.0, 3,680 +/- 551, and 2,552 +/- 627 micrograms/ml in serum, choledochal bile, and gallbladder bile, respectively.

Ampicillin↗
PubMed1984

Biliary excretion of ceftizoxime in humans.

Biliary concentrations of a new cephalosporin, ceftizoxime, were measured in bile collected in 8 cholecystectomized patients provided with T-tube drainage and in 14 patients where bile was obtained by puncture of the gall bladder and choledochus during cholecystectomy. In patients with external biliary drainage, a mean biliary peak of 150.3 +/- SEM 49.8 micrograms/ml has been observed 2 h after intravenous injection of 2 g of ceftizoxime; the antibiotic activity amounted still to 17.3 +/- 6.0 micrograms/ml after 6 h. Assays performed during operation showed the following simultaneous concentrations 1 h after 2 g of ceftizoxime given intravenously: serum: 85.3 +/- 8.1 micrograms/ml; main duct bile: 279.8 +/- 40.0 micrograms/ml; gallbladder bile: 119.9 +/- 19.4 micrograms/ml. These findings were compared with the biliary excretion of 8 other cephalosporins studied previously under the same conditions. The results of the present study suggest that administration of ceftizoxime may be effective in the treatment of biliary tract infections.

Bile↗
PubMed1984

Effect of middle-term gliclazide treatment on insulin secretion in non-insulin dependent diabetics.

Insulin secretion was studied in 12 non-insulin dependent diabetics during middle-term administration of the sulphonylurea gliclazide. Blood sugar, C-peptide and glucagon were also estimated during the intravenous glucose tolerance and arginine tests performed before and after therapy. After 3 months of gliclazide therapy (240 mg/day) in addition to a low carbohydrate diet, the intravenous glucose tolerance test showed a significant reduction in blood sugar levels and in the partial and total areas under the blood sugar curve, as well as an improvement in early insulin secretion, characterized by a significant increase in plasma C-peptide at 4, 10 and 20 minutes. Plasma glucagon levels were not affected by the sulphonylurea therapy. In the arginine test, blood sugar levels were lower at the end of the treatment period; plasma insulin, C-peptide and glucagon did not change significantly. In this study, plasma C-peptide has proved to be a better indicator of stimulated insulin secretion than plasma insulin levels. The scarcity of hypoglycaemic episodes during therapy with gliclazide may be related to the selective stimulation of early insulin secretion by this drug.

Adult↗
PubMed1984

[Evaluation of the biliary passage of beta-lactam antibiotics].

The present study is devoted to the biliary excretion of some beta-lactam antibiotics (6 derived from the penicillin group: Penicillin G, Ampicillin, Metampicillin, Carbenicillin, Mezlocillin, Apalcillin and 9 from the cephalosporin group: Cephalothin, Cephaloridine, Cephacetrile, Cefalexin, Cefazolin, Cefamandole, Cefuroxime, Cefaclor and Ceftizoxime). The biliary excretion of these antibiotics was assessed by 4 different procedures: 1) experimental study of their biliary elimination by a perfused isolated rabbit liver; 2) in humans, by evaluation of their passage: a) in aspirated duodenal fluid, b) in bile collected by external biliary drainage, c) and in bile obtained by puncture of the main bile duct and the gall bladder during surgery. The results of these different investigations were concordant and showed that the biliary excretion of Metampicillin, Apalcillin and Mezlocillin was definitely higher than that of the other studied beta-lactams; on account of their suitable antibacterial spectrum, these 3 derivatives should be used in preference for the treatment of biliary infection.

Animals↗
PubMed1983

Biosynthetic human insulin: pharmacokinetics and effects in healthy human volunteers.

The pharmacokinetics and pharmacodynamics of intravenously injected biosynthetic human insulin (0.06 U/kg) and purified pork insulin, both regular, were compared intraindividually in ten presumably healthy volunteers. Some of the pharmacokinetic parameters, e.g., the area under the insulinemia curve, the total plasma clearance, and insulin bioavailability, were similar, whereas insulin biologic half-life appeared to be longer and the apparent volume of insulin distribution larger with BHI. No appreciable difference between the two insulins was observed as far as their hypoglycemic effect and secretory inhibition of endogenous insulin (expressed as C-peptidemia) were concerned, but reactive hyperglucagonemia was found to be less with BHI than with PPI. These findings are discussed in the light of our current knowledge of BHI.

Adult↗
PubMed1982

[Pharmacokinetics of intramuscular mezlocillin in patients with normal and impaired renal function (author's transl)].

Pharmacokinetic values of mezlocillin were determined after a single intramuscular injection of 1 g to 10 subject with normal renal function, 10 patients with stable renal insufficiency and 5 patients with chronic renal failure under long-term haemodialysis. The values obtained in normal subjects were : biological half-life Tb 1/2 0.9 hour; elimination constant Ke 0.790 (h-1); total clearance Ct 449 ml/min/1.73 m2; renal clearance Cr 263 ml/min/1.73 m2. Twelve hours after the injection 72.2 % of the dose administered were recovered in the urine. Theoretical values after repeated injection were calculated from the values obtained in subjects with normal renal function. The loading doses providing steady state serum concentrations were determined for various dosage intervals (2, 3, 4, 6 and 8 hours). In patients with renal insufficiency or treated with haemodialysis, serum levels decreased more slowly. The theoretical Tb 1/2 for zero creatinine clearance was 4.7 hours. Sixty-two percent of the amount of mezlocillin present in the central compartment at the onset of haemodialysis were removed after a 6-hour dialysis session. In all 25 subjects investigated, a significant correlation was found between Ke and Ccr (Ke = 0.1973 + 0.0046 Ccr). This correlation was used to calculate the loading and maintenance doses (and sometimes also the intervals between injections) adjusted to renal function values. Dosage guidelines in relation to the renal function were established from these data.

Humans↗
PubMed1982

[Comparative biliary excretion of mezlocillin and 12 other beta-lactam antibiotics (author's transl)].

The biliary excretion of mezlocillin was studied on an experimental in vitro model (perfused rabbit liver) and by various methods in man. After addition of 10 mg mezlocillin to blood perfusing isolated rabbit lever preparations (n = 5) during 3 hours, a mean biliary peak of 758 +/- 129 micrograms/ml was recorded between 30 and 60 minutes. The 0-3 h cumulative biliary excretion was 20.3 % of the dose administered. Following a 30 min intravenous infusion of 5 g mezlocillin to 5 healthy subjects, the mean maximal antibiotic activity in the duodenal aspiration fluid was 626.0 +/- 115.0 microgram/ml during the first hour. In 10 cholecystectomized patients with T-tube drainage who received 1 g mezlocillin intramuscularly, a mean biliary peak of 296 +/- 58 micrograms/ml was recorded. The 0-12 h cumulative biliary excretion of the antibiotic was 2.6 % of the dose injected. After intravenous infusion of 5 g mezlocillin, the corresponding values were 505 +/- 118 micrograms/ml and 1.3 % respectively. One hour after rapid intravenous injection of 2 g mezlocillin, the antibiotic activities in samples of serum, common bile duct bile and gallbladder bile collected during cholecystectomy were 28.9 +/- 5.3, 895 +/- 196.1 and 402 +/- 133.2 micrograms/ml respectively. These results were compared with those obtained in similar conditions with 12 other beta-lactam antibiotics.

Animals↗
PubMed1982

Biliary excretion of cefaclor. Experimental and clinical study.

Biliary excretion of cefaclor, a new orally active cephalosporin, was studied in vitro using an isolated rabbit liver preparation perfused for 3 h (n = 5). Under these conditions, bile recovery amounted to 2.3% of the cefaclor dose added to the circulating blood (10 mg). In humans, after oral administration of a 1-gram dose of cefaclor to cholecystectomized patients provided with a T tube (n = 10), a mean biliary peak concentration of 7.6 +/- 2.4 microgram/ml was observed at the 3rd hour. Cumulative biliary excretion amounted to 0.05% of the administered dose. Assays performed on samples collected during cholecystectomy in 10 patients 1 h after intake of a 1-gram dose of cefaclor showed mean concentrations of 13.7 +- 1.2 micrograms/ml in serum, 8.1 +/- 1.3 micrograms/ml in common duct bile and 5.9 +/- 1.4 micrograms/ml in gallbladder bile. These results were compared with the data obtained after administration of seven other cephalosporins studied under identical conditions.

Adult↗
PubMed1982

Pharmacokinetics of mezlocillin in patients with kidney impairment: special reference to hemodialysis and dosage adjustments in relation to renal function.

The pharmacokinetics of Mezlocillin were determined after the intramuscular injection of a single 1-gram dose in 10 subjects with normal renal function, in 10 patients with stabilized renal impairment and in 5 patients with end-stage renal disease submitted to repeated hemodialysis. In normal subjects, biological half-life, Tb1/2, was equal to 0.9 h; total clearance (Ct) to 449 ml/min/1.73 m2; renal clearance (Cr) to 263 ml/min/1.73 m2.72.2% of the administered dose was excreted in the urine within 12 h. In patients with renal insufficiency and in patients undergoing long-term hemodialysis, the serum concentration decrease was markedly slower. During a 6-hour dialysis session, 62% of the Mezlocillin present in the central compartment at the start of hemodialysis was removed. In the 25 subjects under study, a significant correlation was found between the values of Ke and those of creatinine clearance, Ccr (Ke = 0.1973+0.0046 Ccr). This relation was used to calculate the loading doses, the maintenance doses and the dosage intervals adjusted to the degree of renal impairment, allowing assessment of useful dosage recommendations.

Anti-Bacterial Agents↗