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J M Brogard

Publications and source records attributed to J M Brogard.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Comparative pharmacokinetic profiles of cinoxacin and pipemidic acid in humans.

Serum and urinary levels of Cinoxacin and pipemidic acid were determined at 7-day intervals in the same 10 healthy volunteers after a single oral dose of respectively 500 and 400 mg of the drugs. Comparison of results shows that Cinoxacin was absorbed faster (absorption half-life, ta 1/2cin = 0.25 h) than pipemidic acid (ta 1/2pip = 0.37 h) and distributed in a smaller apparent volume (AVDcin = 23.5 1/1.73 m2; AVDpip = 60.1 1/1.73 m2). Biological half-lives were identical (tb 1/2cin = 2.10 h; tb 1/2pip = 2.15 h). On the other hand, serum levels for Cinoxacin at 1, 2 and 4 hours (8.1 +/- 1.5 micrograms/ml, 10.6 +/- 1.5 micrograms/ml, 5.6 +/- 1.3 micrograms/ml respectively) were higher than those for pipemidic acid (3.3 +/- 0.3 micrograms/ml, 3.4 +/- 0.5 micrograms/ml, 2.1 +/- 0.5 micrograms/ml respectively). Urinary excretion of the two derivatives during the 12 hours following their administration was similar (Ucin0-12h = 86%; Upip0-12h = 83%). Mean urinary concentrations were particularly high, still attaining respectively 90 +/- 29 micrograms/ml and 131 +/- 38 micrograms/ml in samples collected between the 9th and the 12th hours; these levels were well above the M.I.C. for the Gram-negative organisms included within the spectrum of activity of these two quinolones. In addition, predictive calculations of serum levels reached after multiple dosing indicate that at an administration rate of 500 mg every 6 or preferably every 4 hours, Cinoxacin concentrations should be sufficiently high to be of interest in the treatment of systemic infections by sensitive organisms.

Administration, Oral↗
PubMedDate not supplied

Ciprofloxacin biliary disposition in cholecystectomised patients with special references to HPLC and bioassay data.

The biliary disposition of ciprofloxacin was studied in 12 recently cholecystectomised patients during 24 hours following a single oral administration of 500 mg of the drug. Ciprofloxacin was measured in serum, urine, bile and faeces by both high performance liquid chromatography (HPLC) and bioassay. The results were found to be comparable for the concentrations in serum (mean Cmax = 0.97 +/- 0.17 microgram/ml by HPLC and 1.08 +/- 0.19 microgram/ml by bioassay) and in urine (0.6 h: 267 +/- 74 micrograms/ml and 241 +/- 58 micrograms/ml respectively). Higher concentrations were found in bile when measured by bioassay compared with HPLC (peak concentration = 10.3 +/- 3.4 micrograms/ml and 7.5 +/- 2.8 micrograms/ml respectively; p less than 0.02). The total biliary elimination was also significantly higher according to bioassay data (2167 +/- 288 micrograms/ml versus 1587 +/- 222 micrograms/ml; p less than 0.01). This suggests a first pass effect and hepatic biotransformation of ciprofloxacin to one or more active metabolite (s).

Administration, Oral↗
PubMedDate not supplied

[Role of polyols in the development of diabetic complications. Value of aldose-reductase inhibitors].

The evidence of sorbitol excess in the crystalline lens of alloxan-diabetic rats has led to anticipate the role of the enzyme aldose-reductase in the pathogenesis of the diabetic cataract. In addition, a number of experimental works have more recently shown the involvement of myoinositol deficiency, which probably results from the sorbitol accumulation. These metabolic pathways are most likely implicated in the pathogenesis of diabetic neuropathy and perhaps additionally in that of microangiopathy. The synthesis of several aldose-reductase inhibitors (AR inhibitors) confirmed experimentally these hypothesis. By reducing the activity of the enzyme aldose-reductase, these substances suppress the adverse metabolic consequences of polyol accumulation, myositol deficiency and dysfunction of the Na+/K+ ATPase dependent sodium activity. Although different experimentations showed that the AR inhibitors could prevent in animals the development of experimental cataract as well as the early functional or later anatomic abnormalities of the diabetic retinopathy and nephropathy, the clinical trials did not clearly support these experimental results in humans. On the other hand, the AR inhibitors were proved to exhibit some efficacy in the early stage of diabetic neuropathy and in incipient nephropathy where they delay the development of albustix positive proteinuria. However, the benefit of an early treatment with AR inhibitors should be confirmed by long term prospective studies, which could also assess the safety of these drugs in chronic administration.

Aldehyde Reductase↗
PubMedDate not supplied

[Alpha-glucosidase inhibitors: a new therapeutic approach in diabetes and functional hypoglycemia].

Acarbose, a potent alpha-glucosidase inhibitor, represents a new concept for the treatment of metabolic disorders, and particularly diabetes mellitus. It slows the absorption kinetics of dietary carbohydrates by reversible competitive inhibition of alpha-glucosidase activity, and so reduces the post-prandial blood glucose increment and insulin response. For these reasons, the drug has been successfully used not only in the treatment of type I or type II diabetes, but also in the management of reactive hypoglycemias and dumping syndrome. In addition, some data suggest a possible role in the treatment of type IV hyperlipidemia. Because of the delay in absorption of oligo- and disaccharides resulting from its administration, a colic bacterial fermentation occurs, accounting for the frequent abdominal discomfort mentioned by the patients. These side effects would be lessened with the second generation glucosidase inhibitors now in progress.

Acarbose↗
PubMedDate not supplied

[Discovery of pancreatic diabetes in Strasbourg].

Although many clinical aspects of diabetes were already known in the second half of the XIXth century, its pathogenesis remained mysterious. The German Medical School of Strasbourg, rich of numerous eminent teachers and researchers such as A. Kussmaul and B. Naunyn in the 1880ies, represented by this time one of the leading centers in diabetes research. The studies of Joseph Freiherr Von Mering on phloridzin-induced glycosuria are an example between others, but the discovery by Oskar Minkowski of the pancreatic origin of the disease undoubtedly stands as the most famous. This discovery was partly indebted to luck since Von Mering and Minkowski were studying a problem of digestive absorption of lipids, but it was greatly due to the excellent clinical and experimental training of Minkowski, as well as his operatory skill. These works, initially criticized by some authors, turned out to stimulate in several countries researchs on the isolation from pancreas of an hypoglycemic substance. Several investigators gave up or failed near the end, which was reached in 1921 by F. Banting and C. Best, subsequently opening the therapeutic era of diabetology.

Diabetes Mellitus, Type 1↗