Effect of pH on the Hydrolysis of Chlorothalonil Aqueous solutions of chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) were prepared at 0.5 ppm, buffered at pH 5 to 9, and stored in the dark. No hydrolysis was observed at pH 7 or lower. At pH 9, chlorothalonil hydrolyzed to 4-hydroxy-2,5,6-trichloroisophthalonitrile and 3-cyano-2,4,5,6-tetrachlorobenzamide. The rate of decline of chlorothalonil followed first-order kinetics and was determined to be 1.8% per day using gas chromatographic and radiotracer techniques.
A long-term evaluation of the therapeutic efficacy and safety of oral almitrine bismesylate (AB) (50 mg twice daily) was made on 25 patients with COPD and moderate hypoxemia residing at an altitude of 1,500 m in a double-blind placebo-controlled study. Thirteen patients receiving AB (baseline PaO2, 54.3 +/- 4.9 mm Hg; mean +/- SD) and 12 patients receiving placebo (baseline PaO2, 53.0 +/- 4.1 mmHg) were periodically followed by arterial blood gas and other pulmonary function studies and plasma levels of AB. Eight patients receiving AB and nine patients receiving placebo were followed for 1 yr; all patients were followed for at least 90 days. AB administration resulted in an increase in PaO2 to 62.2 +/- 9.3 mm Hg (p less than 0.01) on Day 28. The increase was maintained until Day 360 (63.8 +/- 4.6 mm Hg; p less than 0.01). The mean plasma concentration of AB on Day 28 was approximately one-half that on Day 90 when the plasma level reached a near maximum. AB was associated with weight loss (five of 13 patients receiving AB lost more than 10% of their baseline body weight) and peripheral paresthesias of the lower extremities (three patients), both occurring at the peak plasma levels of the drug. We conclude that AB causes a long-term improvement in arterial oxygenation in hypoxemic patients with COPD residing at an altitude of 1,500 m. Our data suggest that lower doses of AB might produce the same effect on PaO2 with less adverse associated effects, and this should be tested in future studies.
GC DETERMINATION OF THIOFANOX RESIDUES tion curves indicate the presence of carboxylate ions that could be explained by the presence of Na salts of some organic acids as impurities.Elementary analyses of the model substance gave the simplest empirical formula of CigH260nN, whereas the empirical formula of the isolate from barley roasted at 250°f or 40 min was found to be CigHgvOnN. Elementary analysis of both the model substance and the isolate from roasted barley indicated that they are of similar composition.The manner by which nitrogen is chemically bound in the brown substance, produced by the process of nonenzymatic browning after the temperature treatment, is not understood. The concentration of the brown substance in roasted barley was unexpectedly high. However, it can be explained by the fact that nonenzymatic browning occurs in two ways. The first occurs from the reaction between amino acid and reducing sugar, and the second occurs from caramelization, which can, but need not, include nitrogen.Isolation of the brown pigments from roasted barley by means of ion-exchange resin Permutit ES confirms that the substance is of an ionic nature and has a negative charge. According to the results obtained from uv and ir spectra (Figures 1 and 2) and from elementary analysis it was concluded that the isolate of the brown substance from roasted barley was of similar composition to the model substance. ACKNOWLEDGMENTThe able technological assays of M. Glogovcan are grate-fully acknowledged.
Bioavailability and bioequivalency studies of almitrine bismesylate from U.S. manufactured film coated, waxed, 50 mg tablets were compared in 34 normal healthy volunteers to 50 mg European film coated, waxed and unwaxed, tablets and a 0.5 per cent (w/v) oral reference solution of almitrine bismesylate in d,l malic acid. The U.S. manufactured formulations were 85.88 and 87.85 per cent of the calculated mean area under the individual concentration-time curve for almitrine bismesylate reference solution compared to 88.40 and 88.86 per cent for the waxed and unwaxed film coated European tablets, respectively. The mean peak plasma concentrations for the U.S. formulations were 176.3 ng ml-1 and 180.1 ng ml-1 compared to 196.3 and 200.1 ng ml-1 for the waxed and unwaxed European formulations, respectively. Mean time to peak plasma concentrations for the two U.S. formulations and the waxed and unwaxed European formulations were 3.22, 3.33, 3.06, and 3.26 h, respectively. In addition, the oral reference solution yielded a mean peak plasma concentration of 222.8 ng ml-1 and a mean time to peak plasma concentration of 2.68 h. Analysis of variance and multiple range comparisons (p less than 0.05) indicated that the tablet formulations were bioequivalent. The results of this study show that the U.S. formulated almitrine bismesylate tablets exceed 85 per cent relative bioavailability with respect to the oral reference solution and are bioequivalent compared to the marketed standard European tablet formulations.
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