Drug In Tablet Form Research Articles

Determination of acetaminophen in human plasma by ion-pair reversed-phase high-performance liquid chromatography. Application to a single-dose pharmacokinetic study.

The determination of acetaminophen in biological samples of humans who have ingested normal and overdosage of the drug is necessary to understand the clinical pharmacokinetics of acetaminophen and to determine its distribution and toxicokinetic parameters. This paper describes a rapid, simple, and sensitive high-performance liquid chromatographic method for determining acetaminophen in human plasma. Acetaminophen is isolated from plasma by adding approximately 200 microL of acetonitrile and 50 mg of solid zinc sulfate to each milliliter of plasma. A short column (60 mm x 4.6 mm) slurry packed with 5.0-microns PRP-1 particles is used with an isocratic elution of 5.0 mM dibasic potassium phosphate and 5.0 mM tetrabutylammonium hydroxide/methanol, 70:30 (v/v). The flow rate is 1.0 mL/min. The acetaminophen peak is detected with a variable wavelength ultraviolet/visible detector at 250 nm and 0.50 to 0.002 AUFS. The analysis time of the assay is less than 15 min, and the limit of detection is 20 ng/mL for an 80-microL injection volume. The pharmacokinetics of acetaminophen in plasma from a subject who had orally ingested 975 mg of the drug in tablet form is conducted using this method, and various pharmacokinetic parameters are determined.

Use of 7,7,8,8-Tetracyanoquinodimethane in the Colorimetric Determination of Some Antihistamines

Abstract A precise colorimetric method is described for the estimation of phenyltoloxamine dihydrogen citrate, diphenhydramine hydrochloride, and chlorpheniramine maleate. The method is based on the interaction of these drugs as n-electron donors with 7,7,8,8-tetracyanoquinodimethane as π-acceptor to give a highly colored radical anion. This is corroborated by electron spin resonance spectroscopy. The colored product is quantitated spectrophotometrically at 843 nm. Beer's law is obeyed in the concentration range 2-6 µg/mL for each drug. Optimization of the experimental conditions is described. The proposed method was applied to the analysis of these drugs in tablet form, and results were in good agreement with those obtained by the official method

Analysis of the metabolites of ethyl loflazepate by gas chromatography with electron-capture detection

A gas chromatographic assay with electron-capture detection (GC—EC) is described for the metabolites of ethyl loflazepate (Victan), a new benzodiazepine with a potent anti-anxiety activity, in biological fluids. Since the parent drug undergoes a first-pass effect, pharmacokinetic data may only be obtained by measuring the total levels of two of the major metabolites. Accurate data can not be obtained for the metabolites separately since one of them (M1) is chemically transformed to the other (M2) during plasma sampling, storage and extraction. A sensitive, specific and accurate GC—EC assay is developed using a synthetic analogue of M2 as an internal standard. The limit of detection in plasma is approximately 2 ng/ml and the precision about 3% (within-run and between-run). The method is applied to plasma samples collected after oral administration of 2 mg and 4 mg of the drug in tablet form to human volunteers. The results obtained are correlated with those from an existing gas chromatographic—mass spectrometric assay. A very good correlation between the results (inter-laboratory comparison) is obtained, validating both techniques.

Colorimetric Determination of Disulfiram in Tablets: Collaborative Study

The colorimetric reaction of cuprous iodide and disulfiram has been collaboratively studied in 8 laboratories to determine the drug in tablet form at 2 dosage levels. The disulfiram was extracted from the tablet matrix with methylene chloride. After a basic wash with 1 M NaOH, an aliquot of the methylene chloride solution was reacted with solid cuprous iodide, and the absorbance of the resulting color was measured. Single assays on 2 synthetic preparations of known disulfiram content were performed with average recoveries of 98.4 and 99.2% for 93.3 and 105.3 mg, respectively. Duplicate determinations on 2 commercial tablet preparations declared at 250 and 500 mg gave mean and standard deviation values of 246.6 +/- 6.40 and 493.6 +/- 12.0 mg, respectively. The results agreed closely with those obtained by the author using the NF iodometric titration procedure. The method has been adopted official first action.

The effect of nitroscanate tablets on Echinococcus granulosus and Taenia hydatigena infections in dogs

Tablets of micronised nitroscanate (nominal particle size 2--3 microns) were given to a total of 190 dogs that had been experimentally infected with either Echinococcus granulosus or Taenia hydatigena. The efficiency of the drug in tablet form in freeing dogs from tapeworms, was investigated. The dose rate at which 50 per cent of normally fed dogs can be expected to be freed from E granulosus was found to be 89 mg/kg (95 per cent confidence limits 55 mg/kg to 140 mg/kg). The 90 per cent effective dose rate was not determined within the range 32 mg/kg to 250 mg/kg. The dose rate at which 90 per cent of normally fed dogs can be expected to be freed from T hydatigena was 37 mg/kg (95 per cent confidence limits 23 mg/kg to 60 mg/kg).

Pharmacokinetics of prazepam in man

An original electron-capture gas chromatographic assay was developed for simultaneous measurement of plasma levels of the benzodiazepine derivative prazepam and of its principal unconjugated metabolite, N-desmethyldiazepam. The assay was used to study the pharmacokinetics of the drug and its comparative bioavailability from tablets and from a specially prepared solution. Nine healthy adult volunteers were studied. Each volunteer on one occasion took 30 mg of the drug in tablet form, and on another occasion 30 mg of the drug in solution. In all subjects, N-desmethyldiazepam appeared in plasma shortly after prazepam appeared and reached a peak within four hours of prazepam ingestion. Thereafter plasma N-desmethyldiazepam levels were much higher than plasma prazepam levels throughout. Prazepam became undetectable within six hours of intake, whereas its metabolite could still be measured in plasma fourteen days after dosage. Thus much of the pharmacological action of prazepam may be mediated through its metabolite, N-desmethyldiazepam. In five of the nine subjects, areas under the plasma level curves for the metabolite were not markedly different for the tablet and solution formulations studied. In the other four subjects the area under the curve for the tablets was 50% to 80% of the area under the curve for the solution. The time to reach peak plasma level for the metabolite was shorter after the solution formulation (mean 2.0±SD 1.2 h) than after the tablet formulation (mean 4.2±SD 1.7 h).

Sodium Cobaltinitrite as a Reagent for Determining Some Phenolic Drugs

Abstract Dichlorophen, oxyphenbutazone, phenazone, methyldopa, isoprenaline sulfate, and salbutamol sulfate are reacted with sodium cobaltinitrite in aqueous acetic acid. The yellow color is measured at 365, 320, 320, 330, 425, and 325 nm in aqueous acetic acid, respectively, and at 445, 380, 375, 345, 325, and 412 nm in sodium hydroxide, respectively. The reaction product is extractable with CHC13, with a maximum absorption at 370 nm for dichlorophen, 355 nm for phenazone, and 325 nm for oxyphenbutazone. The method is applied to the determination of these drugs in tablet form. The results obtained are reasonably reproducible with a coefficient of variation less than 2%.

Probucol: A new cholesterol‐lowering drug effective in patients with type II hyperlipoproteinemia

Type II hyperlipoproteinemia or hyperbetalipoproteinemia (B-HLP), a condition with considerable atherogenic potential, is one of the most difficult lipid disorders requiring treatment. Since this abnormality responds minimally to dietary therapy alone, supplemental drug therapy is usually essential. Although the available bile-sequestering resins are effective in B-HLP, these substances are unpalatable and constipating. Since lifelong drug therapy is necessary as an adjunct to diet in the treatment of B-HLP, the ideal drug should be both effective and well tolerated. Probucol, a new cholesterol-lowering drug in tablet form without serious adverse effects, was evaluated in a 12-wk double-blind crossover trial in 11 patients with B-HLP whose serum cholesterol levels were in excess of 275 mg/dl. Probucol, in a dosage of 500 mg twice daily, produced a 10% or greater reduction in serum cholesterol levels in all 11 patients. Serum cholesterol was lowered (p less than 0.01) from 353 to 291 mg/dl in the entire group receiving probucol. There was no significant change (p greater than 0.1) in serum cholesterol (352 mg/dl) during placebo administration. These were no untoward drug effects during the study, and all patients maintained excellent complicance to the schedule of medication. These results indicate that probucol possesses considerable cholesterol-lowering activity and may be a promising new nontoxic therapeutic agent in type II hyperlipoproteinemia.

Bioavailability of Aspirin from Commercial Suppositories

A comparison of the bioavailability of salicylate from five brands of commercially available aspirin rectal suppositories in an adult panel is presented. All brands show slow absorption compared to oral administration of the drug in tablet form. At best, about 40% of the dose (on the average) was absorbed when retention time in the bowel was limited to 2 hr. However, four out of the five brands gave substantially lower absorption rates so that only about 20% of the aspirin is available.

An assessment of metronidazole in the treatment of acute ulcerative pseudomembranous gingivitis (Vincent's disease)

The need for a simple and safe drug in tablet form for the treatment of Vincent's disease has been discussed, and the literature on the use of metronidazole for this purpose has been reviewed. Age distribution, main complaints, and some possible etiologic factors in fifty patients with Vincent's disease have been given. The treatment of these fifty patients with metronidazole has been described, and the results of this treatment have been assessed.