Pulse assessment and ABPI have limited utility in the detection of peripheral artery disease in people with diabetes foot ulceration. TBI and distal tibial waveforms are useful for selecting those needing diagnostic testing.
The metabolism of fenfluramine in man results in the excretion of unchanged fenfluramine, deethylated fenfluramine, and m-trifluoromethylhippuric acid. Methods are described for the determinations of these three compounds and the total metabolites in urine by GLC. The m-trifluoromethylhippuric acid accounts for 66 to 9 3 percent of the dose and 79 to 100 percent of the dose may be accounted for as these three metabolites.phenethylamine hydrochloride] is an effective anorexigenic agent showing little or no CNS stimulant properties (1). Structurally, this compound is similar to the amphetamines.Duhault and Fenard (2) have reported a study of the excretion, distribution, and metabolism of fenfluramine using methyl orange complex for its determination. They found that fenfluramine persists in the animal body for considerably longer than amphetamine. The total excretion following oral doses in man and in dogs was 2 i to 380/, of the dose over a 5-to 6-day period.Relatively large amounts were found in fatty tissues of the dog. These authors found that the drug is deethylated but could find little or no evidence for hydroxylation, as occurs with amphetamine. Beckett and Brookes (3), using gas chromatographic methods, have studied the dependence of the rate of excretion on urinary pH. They found that some 50% of feduramine was excreted unchanged or deethylated under acidic urinary conditions, but could account for only 6 to 23y0 with uncontrolled acidity of the urine. The relatively low recoveries of the amines, which has been confirmed in these laboratories, led the authors to investigate the fate of the remainder of the drug in the animal body. Extensive use of gas chromatography in these studies was made to determine the amounts of unchanged drug and its metabolities in biological materials. Blood levels in man and the dog have been determined by GLC. The results given below indicate that the major portion of an oral dose of fenfluramine in man is excreted as m-trifluoromethylhippuric acid (Scheme I). EXPERIMENTAL.Human Study-Two normal, healthy males were given a 60-mg. tablet of fenfluramine as a single dose, and urine was collected at intervals for 72 hr. Ammonium chloride was administered the previous day and throughout the period of urine collection, . tories, A. H. Robins Company, Inc.. Richmond, V A 23220 in an attempt to maintain an acidic urine. All urine samples were kept in the refrigerator until analysis. The pH of each sample was determined with a pH meter immediately upon receipt. Blood samples of 20 ml. were collected at intervals during the first 8 hr. for analysis.Dog Study-A mongrel male dog weighing 11.7 kg. was given a divided oral dose of 117 mg. of fenfluramine, and urine was collected for 5 days and stored under refrigeration.Materials-rn-Trifluoromethylbenzoic acid was purchased from J. T. Baker Chemical Co. m-Trifluoromethylhippuric acid was prepared by reaction of m-trifluoromethylbenzoic acid with thionyl chloride to give m-trifluoromethylbenzoyl chloride. The acid chloride was then reacted ...
For the volume of reaction zone in this study the incident flux is therefore 7.36 x 1 0 ' 8 photons/min. This is a reasonably large value for a low-pressure lamp and demonstrates the benefits of the long length and close proximity of the reaction zone and source; the aluminum reflector also increases the intensity.Figure 2 also demonstrates the good agreement between theory and experiment. By taking the value of 10 calculated from the initial slope of Figure 2, using the molar absorptivity at 254 nm (Table I), and assuming that the i.d. of the tubing, 0.6 cm, is b, one calculates that the exponential term becomes significant at an iron(III)-oxalate concentration of 2.65 mM. For the concentration of generator used here, 4.18 mM, deviation from linearity should occur at about 65 photoconversion. This is the case as can be seen in Figure 2. It would be possible to construct a sliding shutter with calibration marks so that a variety of titrant concentrations could be selected with a single flow rate, thus eliminating the need for a variable pump.Some conclusions can be drawn regarding the practical value of external photochemical generation. First, it is clear that reproducible flow rates and lamp intensity can be obtained with reasonable care. Second, it is possible to obtain a sufficient intensity from a low-power lamp to generate useful titrant concentrations, and the intensity is constant over many months of continuous operation. It should be noted that in situ titrations employ medium-pressure lamps which must be turned off when not in use ( I , 2). Finally, the titrant concentration can be easily changed by changing the length of the photolytic reaction zone.A NUMBER OF METHODS have been presented during recent years for the determination and identification of amphetamine and its derivatives in urine. These methods are based primarily on GLC (1-3) and TLC (4-7) or specific color reactions (8, 9). However, none of these procedures are applicable to the determination of these drugs in blood because of their lower limits of detection. Axelrod (IO) adapted a nonspecific colorimetric procedure to the determination of amphetamine in plasma and tissues of animals that received relatively large doses.The method described below is based on the formation of the heptafluorobutryl derivatives of four of these amines and their subsequent determination by GLC using an electroncapture detector. Halogenated amide and ester derivatives prepared from amines and alcohols usually give high sensitivity with the electron-capture detector. A number of these were prepared and from the results obtained it appeared that the heptafluorobutyramides gave the best results.(1) A.(4) B. Davidow, Psychopharmucol. Bull., 3, 30 (1966). ( 5 ) H. Eberhardt and M. Debackere, Armeim.-Forsch., 15, 929 (6) M. Debackere and A. M. Massart k e n , Arch. Intern. Phar-(7) M. L. Weischer and K. Opitz, Arzneim.-Forsch., 17, 625 ( 8 ) M.
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