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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 4 (1987), S. 348-352 
    ISSN: 1573-904X
    Keywords: hydrochlorothiazide ; triamterene ; Dyazide ; Maxzide ; amiloride ; Moduretic ; food–drug interactions ; food-formulation interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The absorption of three combination formulations of hydrochlorothiazide and either triamterene or amiloride was studied over a 5-year period in seven separate investigations under varying conditions of food and fasting. The most widely prescribed combination, containing 25 mg of hydrochlorothiazide and 50 mg of triamterene, demonstrated impaired absorption in the fasting state that was partially corrected by the addition of a breakfast high in fat. The increase in the fat content of the food appeared to correlate directly with the amount of both drugs absorbed from this formulation. The second formulation studied, a new combination formulation of 50 mg of hydrochlorothiazide and 75 mg of triamterene, demonstrated acceptable absorption in the fasting state that was not altered by the concurrent administration of a high-fat breakfast. The absorption of the third formulation, a combination of 50 mg hydrochlorothiazide and 5 mg amiloride, was acceptable in the fasting state and demonstrated a slight reduction in the absorption of the amiloride component when administered concurrently with a high-fat meal. The clinical and biopharmaceutic implications of these observations are discussed.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 8 (1991), S. 744-749 
    ISSN: 1573-904X
    Keywords: nitroglycerin ; nitroglycerin metabolites ; bioequivalence ; transdermal drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We recently compared plasma concentrations of nitroglycerin and its two dinitrate metabolites in 16 healthy male subjects after application of two controlled-release transdermal formulations of the drug. Analysis of the resulting plasma concentration–time curves indicated that the two formulations did not produce equivalent concentrations of parent drug or either of the dinitrate metabolites during the initial period of dosing. In addition, both formulations produced concentrations of the two dinitrate metabolites that exceeded the concentration of the parent drug by severalfold. Even if the pharmacologic effect of the dinitrate metabolites is low compared to that of nitroglycerin, these higher concentrations may contribute to the effect of nitroglycerin. Scrutiny of the ratio of 1,2-glyceryl dinitrate to 1,3-glyceryl dinitrate in the 16 subjects confirmed previous observations that preferential formation of the 1,2-glycerol dinitrate metabolite may occur depending on the route of administration. This ratio may thus be indicative of the bioavailability of nitroglycerin following transdermal application. Additional data suggesting racial differences in nitroglycerin absorption after transdermal application are presented.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 6 (1989), S. 125-132 
    ISSN: 1573-904X
    Keywords: stereospecific assay ; benoxaprofen ; glucuronides ; enantiomers ; diastereoisomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The diastereoisomeric glucuronic acid conjugates of R/S-benoxaprofen are the major benoxaprofen metabolites and are found in urine at high concentrations. The conjugates of R- and S-benoxaprofen can be separated directly on a C18 reversed-phase column using a mixture of acetonitrile and tetrabutylammonium hydroxide buffer, pH 2.5 (28:72, v/v), as the mobile phase. The k′ values of S- and R-benoxaprofen glucuronides are 57.5 and 63.0, respectively. Diluted urine or deproteinized plasma samples were injected without further treatment. With fluorescence detection at 313/365 nm, quantifiable limits of 50 ng equiv./ml were found for the conjugates. The intra- and interday variability was below 12%. Utilizing this analytical procedure it is possible to characterize enantioselective glucuronidation both in vivo and in vitro. For in vitro procedures, apparent rates of formation and the R/S ratio may be substrate (benoxaprofen) and cosubstrate (UDPGA) dependent. Moreover, enantioselective cleavage of the formed benoxaprofen glucuronides by alkaline hydrolysis, hydrolytic enzymes, and acyl migration must be controlled for both in vitro and in vivo studies since R-benoxaprofen glucuronide is degraded faster than the S-diastereomer under certain conditions.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Keywords: triamterene ; sulfate conjugate ; protein binding ; blood/plasma ratio ; renal clearance ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic profiles of triamterene and hydroxytriamterene sulfuric acid ester, the major metabolite of triamterene, were studied in six normal male volunteers using a newly developed specific HPLC analytical method. Following a 100 mg oral dose of triamterene, the plasma concentration time course of the sulfate conjugate parallels that of triamterene in all subjects, but concentrations of the metabolite were more than 10 times higher than unchanged triamterene concentrations at identical sampling times. Interestingly, the renal clearance of the sulfate conjugate was less than that of triamterene. These characteristic features of triamterene disposition were fitted to a compartment model incorporating a first-pass metabolic process. Unbound fractions of triamterene and metabolite in plasma were 0.39 and 0.10 (mean of 6 subjects), respectively. The low unbound fraction of the metabolite in plasma most probably accounts for the low renal clearance of the sulfate conjugate as compared with triamterene.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Keywords: cefamandole ; cephalosporins ; three-compartment model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A pharmacokinetic study was carried out on six normal healthy adults with average creatinine clearances ranging from 94.8 to 129.3 ml/min. Cefamandole, 15 mg/kg, was administered intravenously over a period of 10 min. Frequent and prolonged samplings of blood and urine were made. Specimens were assayed by a sensitive, accurate, and reproducible HPLC assay. An excellent computer fit to a threecompartment body model was observed. T1/2 α, β, and γ were 5.1, 23.6, and 74.2 min, respectively. The relatively long terminal T1/2 and the area under the curve (AUC) contributed by the γ phase being 31% suggest that a multicompartmental kinetic nature of cefamandole cannot be ignored. Volume of distribution (VDSS)averaged 11.8 liters, and the serum clearance was 200 ml/min. Ninetysix percent was excreted in the urine, and therefore a very high urinary concentration was achieved. The concentration in the plasma exceeds the MIC of many grampositive and negative organisms for many hours.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Keywords: furosemide ; indomethacin ; prostaglandin ; pharmacokinetics ; pharma-codynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four normal males in a crossover fashion with and without indomethacin pretreatment. In each study 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and indomethacin were measured using HPLC; urinary sodium was measured by flame photometry. Pretreatment with indomethacin resulted in increased and prolonged furosemide plasma levels, increased area under the curve, decreased plasma clearance, decreased renal clearance, increased half-life, no change in volume of distribution, and decreased sodium excretion and urine volume. Analysis of sodium excretion rate with time shows that the inhibiting effect of indomethacin was greater during the first 2 hr than at later times.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Keywords: hydrochlorothiazide ; triamterene ; hydroxytriamterene sulfate ; pharmacokinetics ; bioavailability ; renal clearance ; interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate were monitored in the plasma and urine of 24 healthy young men taking single doses of a liquid preparation containing both hydrochlorothiazide and triameterene, liquid preparations containing either of these drugs alone, and a combination tablet recently formulated with a dose ratio of hydrochlorothiazide: triamterene (1∶1,5) found to give optimal potassium-sparing effect. In contradiction to a recent publication, no interaction between the drugs affecting the bioavailability or renal clearance of either could be demonstrated. The previous report of drug-drug interaction probably arose from formulationrelated problems with bioavailability from the two capsule and two tablet products which had been studied. A well-formulated hydrochlorothiazide-triamterene combination tablet promotes plasma concentrations and urinary excretion of hydrochlorothiazide, triamterene, and hydroxytriamterene sulfate which are virtually identical to those seen after either a combination liquid dosage form or simple liquid forms containing only one of the two drugs.
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 10 (2004), S. 638-642 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Thyroxine (T4) is the predominant form of thyroid hormone (TH). Hyperthyroidism, a condition associated with excess TH, is characterized by increases in metabolic rate, core body temperature and cardiac performance. In target tissues, T4 is enzymatically deiodinated to 3,5,3′-triiodothyronine ...
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