Repeated Administration of SL 84.0418, a New Oral Antihyperglycaemic Agent

1995 ◽  
Vol 9 (4) ◽  
pp. 191-196
Author(s):  
F. De Ponti ◽  
F. Crema ◽  
L. DʼAngelo ◽  
M. Caravaggi ◽  
G. Broccali ◽  
...  
Author(s):  
Julio H. Garcia ◽  
Janice P. Van Zandt

Repeated administration of methyl alcohol to Rhesus monkeys (Maccaca mulata) by intragastric tube resulted in ultrastructural abnormalities of hepatocytes, which persisted in one animal twelve weeks after discontinuation of the methyl alcohol regime. With dosages ranging between 3.0 to 6.0 gms. of methanol per kg. of body weight, the serum levels attained within a few hours averaged approximately 475 mg. per cent.


2000 ◽  
Author(s):  
M. C. Oterino ◽  
I. Moragrega ◽  
P. Vicens ◽  
M. C. Carrasco ◽  
R. Redolat ◽  
...  

1995 ◽  
Vol 74 (06) ◽  
pp. 1452-1456 ◽  
Author(s):  
Johannes Treib ◽  
Anton Haass ◽  
Gerhard Pindur ◽  
Ulrich T Seyfert ◽  
Wolfgang Treib ◽  
...  

SummaryThe plasma clearance of hydroxyethyl starch (HES) depends on the initial molecular weight and the degree of substitution. So far, little attention has been paid to the clinical relevance of the C2/C6 substitution ratio of hydroxyethyl starch.10 patients with cerebrovascular circulatory disturbance received hemodilution therapy for 10 days, consisting of 10% HES 200/0.5 (mean molecular weight 200 kD, degree of substitution 0.5) with a C2/C6 ratio of 13.4. A second group of 10 patients received a starch solution with identical initial molecular weight and degree of substitution but with a C2/C6 ratio of 5.7.After the administration of a single dose, no significant differences between the two groups were observed. After repeated administration, significant differences could be detected in hemorheology, coagulation and elimination (p<0.01). The larger C2/C6 ratio led to a higher intravascular mean molecular weight (95 vs. 84 kD), which in turn led to a higher increase in serum concentration during the therapy (14.7 vs.8.6 mg/ml). Hematocrit was lowered more (-30,5 vs. -23,5%) and plasma viscosity was increased more. There was also a more pronounced increase in partial thromboplastin time (+30% vs. +13%) and a factor of 2 larger decrease of factor VIII/von Willebrand factor-complex (p <0.01), which exceeded the dilution effect.The higher C2/C6 ratio of HES 200/0.5/13.4 slows down enzymatic degradation. After repeated administration of this starch, large molecules accumulate which are inefficiently degraded. The same effect has been observed after therapy with highly-substituted HES. This accumulation of large molecules leads to a beneficial longer lasting volume effect. The disadvantages include an increase in plasma viscosity and coagulation disturbances, which cannot be explained with the respective dilution effect alone. For these reasons, the C2/C6 ratio is of clinical relevance and should be included in the product labeling in the future.


1969 ◽  
Vol 21 (02) ◽  
pp. 320-324 ◽  
Author(s):  
K Seiler ◽  
F Duckert

SummaryA case of severe Marcoumar intoxication is described. Eleven hours after the intake a plasma concentration of 15.75 µg/ml was found which corresponds approximately to the 5-fold therapeutic concentration. Repeated administration of vitamin K1 made it possible to avoid extreme lowering of the activity of the clotting factors II, VII and X and to prevent bleeding. Side effects were not observed. The biologic half-life of Phenprocoumon has been found to be shortened at high plasma concentration (3.7 instead of 5.9 days). It is probable that in extreme concentration the drug is less strongly bound to the plasma proteins.


1967 ◽  
Vol 18 (01/02) ◽  
pp. 057-065 ◽  
Author(s):  
G Zbinden

SummaryIntravenous injection of 0.5% lauric acid solution into rabbits caused moderate to marked thrombocytopenia. With small doses (2.5 mg/kg) this thrombocyte decrease was reversible and microscopically demonstrable thrombosis in the lungs was only seen or suspected in a small number of rabbits 10 to 30 min after lauric acid injection. High doses were followed by partly reversible thrombocytopenia and by moderate to marked, sometimes lethal, thrombosis in the lungs still demonstrable 24 hrs after injection. Repeated administration of small doses of lauric acid did not lead to a depletion of the circulating thrombocytes. Thrombocytopenic response, however, appeared to be less pronounced after the second and subsequent injections. Studies with Cr51-labeled platelets indicate that during the reversible thrombocytopenia following a small intravenous dose of lauric acid platelets are retained in various organs, particularly the lungs.


1996 ◽  
Vol 82 (1) ◽  
pp. 147-152 ◽  
Author(s):  
Douglas Vickers ◽  
Charles Pearce

Trail-making tests such as Oswald and Roth's 1987 Zahlen-Verbindungs-Test offer sensitive and reliable indicators of cognitive efficiency that are also simple, inexpensive, and quick to administer. A disadvantage is that there exist only a limited number of test forms so the scope for repeated administration and systematic investigation is restricted. The basic reason is that the principled generation of such pathways remains an unsolved analytical problem. In this note we propose an heuristic stratagem for the generation of alternative test forms for the Zahlen-Verbindungs-Test.


Author(s):  
Anamika Saxena Saxena ◽  
Santosh Kitawat ◽  
Kalpesh Gaur ◽  
Virendra Singh

The main goal of any drug delivery system is to achieve desired concentration of the drug in blood or tissue, which is therapeutically effective and nontoxic for a prolonged period. Various attempts have been made to develop gastroretentive delivery systems such as high density system, swelling, floating system. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The floating or hydrodynamically controlled drug delivery systems are useful in such application. Background of the research: Diltiazem HCL (DTZ), has short biological half life of 3-4 h, requires rather high frequency of administration. Due to repeated administration there may be chances of patient incompliance and toxicity problems. Objective: The objective of study was to develop sustained release alginate beads of DTZ for reduction in dosing frequency, high bioavailability and better patient compliance. Methodology: Five formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters and compared. Alginate beads were prepared by ionotropic external gelation technique using CaCl2 as cross linking agent. Prepared beads were evaluated for % yield, entrapment efficiency, swelling index in 0.1N HCL, drug release study and SEM analysis. In order to improve %EE and drug release, LMP and sunflower oil were used as copolymers along with sodium alginate.


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