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D Westerlund

Publications and source records attributed to D Westerlund.

68 records · Page 4Linked to original sources

Determination of amoxicillin in body fluids by reversed-phase liquid chromatography coupled with a post-column derivatization procedure.

Quantitative methods for determination of amoxicillin in body fluids are described. They comprise separation by reversed-phase chromatography (LiChrosorb RP-8, 5 micron) of the aqueous supernatants obtained from plasma or urine after purification steps involving protein precipitation followed by extraction in the case of plasma, or a double extraction procedure in the case of urine, post-column derivatization with air segmentation, and finally measurement of the UV absorbance at 310 nm. The derivatization involves formation of the mercuric mercaptide of penicillenic acid and is specific for compounds with an intact penicillanic acid ring system. Detection limits achieved on injecting 200 microliter of plasma and 20 microliter of urine are about 25 ng/ml and 200 ng/ml, respectively, but it is possible to improve the sensitivity further by injecting larger volumes. Precisions (srel) obtained for determination of 0.10 and 0.45 migrogram/ml in plasma were 3.72 and 1.40%, respectively. Some problems regarding column stability originating from the injection of biological samples are discussed.

Amoxicillin↗

Absorption and elimination of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): comparison between young and elderly subjects.

The single-dose kinetics of D-propoxyphene, acetyl salicylic acid and phenazone, given in a combination tablet (Doleron), were compared in young and elderly subjects. Serial blood samples were taken 0--48 hours after administration. The plasma concentrations of propoxyphene and of its major metabolite, norporpoxyphene, were assessed by mass fragmentography, those of phenazone by gas chromatography, and those of acetyl salicylic acid plus salicylic acid by spectrofluorometry. Neither for propoxyphene, norpropoxyphene, acetyl salicylic acid nor phenazone did the areas under the concentration curves or the elimination half-lives differ between young and elderly subjects. These data do not provide pharmacokinetic support for a general reduction of the Doleron dosage in elderly subjects.

Administration, Oral↗

Bioavailability of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): interindividual variation and influence of food intake.

The influence of food intake on the bioavailability of three analgesic compounds--propoxyphene chloride, acetyl salicylic acid and phenazone--in a combination tablet, Doleron, has been examined in eight healthy volunteers. A single oral dose was given both on an empty stomach and together with a standardized breakfast meal. The plasma concentrations of propoxyphene, its major metabolite norpropoxyphene, salicylic acid and phenazone were determined by mass fragmentography, spectrofluorimetry and gas chromatography. Concomitant food intake had no consistent influence on the bioavailability of any of the components. Hence, doleron may be taken together with meals as well as between meals. Large interindividual variations in propoxyphene and phenazone concentrations were found, indicating that an optimal effect will not always be obtained by standard doses.

Adult↗

Clinical pharmacokinetics of co-trimazine.

The clinical pharmacokinetics of co-trimazine (trimethoprim plus sulphadiazine) are reviewed and compared with those of co-trimoxazole (trimethoprim plus sulphamethoxazole). Both combination drugs have similar serum half-life values in persons with normal renal function (half-life of 8 to 12 hours), but the sulphamethoxazole metabolites are retained more than trimethoprim in reduced renal function. Sulphadiazine is less metabolised and the total sulphonamide load of therapeutic doses of co-trimazine is therefore less than for co-trimoxazole. Both co-trimazine and co-trimoxazole have high bioavailability. A suspension of co-trimazine gives serum concentrations comparable with those of tablets. The extravascular penetration of the co-trimazine components is reflected by the total area under the lymph concentration curve in comparison with serum. This measure shows a penetration into peripheral human lymph of 68% for sulphadiazine and 59% for trimethoprim. The proportions eliminated in urine are about 55% for sulphadiazine, 30% for its acetylated metabolite and 75% for trimethoprim. In comparison, for co-trimoxazole, the proportion of sulphamethoxazole eliminated in urine is 15%, that of the acetylated derivative 47%, and that of trimethoprim is also 75%. Urine concentrations of both combinations have similar bioactivity against urinary pathogens after 500 mg of co-trimazine and 960 mg of co-trimoxazole.

Aging↗

In vitro-in vivo evaluation of bacampicillin hydrochloride from microcapsules of water-insoluble and an acid-soluble polymer.

Bacampicillin hydrochloride has been microencapsulated to mask its very bitter taste. The objective of the study was to compare the in vitro release and bioavailability of bacampicillin hydrochloride from microcapsules coated with two principally different polymers: a water-insoluble polymer, ethylcellulose, and an acid-soluble polymer, Eudragit E 100. The last mentioned was supposed to have advantages from a bioavailability point of view since this polymer should dissolve rapidly upon reaching the stomach. In vitro release studies were performed in different types of media by using a flow-through cell technique and USP paddle apparatus. The in vivo study was performed on 20 healthy volunteers taking single 400 mg doses of the drug in the two microcapsule suspensions and a reference tablet according to a randomized cross-over design. When standard dissolution fluids were used, the Eudragit E 100-coated microcapsules revealed very rapid dissolution but were greatly dependent on buffer concentration and ionic strength. The ethylcellulose-coated microcapsules released the drug much more slowly than Eudragit E 100 when using standard dissolution fluids. They were also affected by buffer concentration and ionic strength. The reference tablet had a significantly higher bioavailability than the two microcapsule suspensions. In vitro-in vivo correlation was not obtained when using standard dissolution fluids according to USP. However when stimulated intestinal fluid was adjusted to have an ionic strength similar to intestinal fluid, a better in vitro-in vivo correlation was obtained. The Eudragit E 100 polymer did not give better bioavailability than ethylcellulose as a coating polymer on bacampicillin microcapsules.

Absorption↗