Sadeq Othman

Spectrophotometric study of the photodecomposition kinetics of nifedipine

Nifedipine is a photosensitive compound. Irradiation for 4 h under a fluorescent lamp placed 30 cm from a solution of nifedipine in 95% ethanol leads to complete photo‐oxidation as determined spectrophotometrically. The disappearance of the reduced form and appearance of the oxidized form is best described by zero‐order kinetics at concentrations higher than 4 times 10−4 M. At lower concentrations pseudo‐first order kinetics are followed. Monochromatic irradiation of nifedipine at wavelengths 400 to 700 nm in 25 nm increments showed no change in the absorbance at 280 nm, and, except for a hyperchromic effect at 237 nm, no other spectral changes were observed. Its photo‐oxidation was dependent on the intensity of light and increased exponentially as solutions were irradiated progressively closer to a fluorescent light source. The pH studies showed that aqueous solutions of nifedipine photo‐oxidized fastest at pH 2.

Changes in glutathione and its metabolizing enzymes in human erythrocytes and lymphocytes with age.

The levels of glutathione (GSH) and the activities of glutathione S‐transferases (GST) and glutathione reductase (GSR) in human erythrocytes and lymphocytes were determined in three age groups (5–12, 25–40, 65–83 years). The levels of GSH in lymphocytes increased with age, however, its levels in erythrocytes reached a maximum in the middle age group. The activity of GST in erythrocytes and lymphocytes changed as a function of age in a pattern similar to the changes found for GSH levels. GSR activity increased from young to middle age in both erythrocytes and lymphocytes, but decreased again in the old age group.

Some factors affecting the photodecomposition of nifedipine

Abstract Nifedipine, like most nitrophenyldihydropyridine derivatives, undergoes rapid photochemical oxidation to the corresponding nitrophenylpyridine when exposed to light. This is accompanied by a remarkable diminution of the pharmacological activity. In this report, the stability of the drug in different organic solvents and in the presence of an antioxidant was investigated. The UV-spectral properties of the oxidized and reduced forms of the drug were similar in acetonitrile, ethanol and chloroform. In cyclohexane the oxidized form showed absorption characteristics different from those in other solvents. Kinetic parameters for the disappearance of the reduced form or the appearance of the oxidized form as a function of bisulfite concentration were determined and the half-lives calculated. The degradation of two structural analogues of nifedipine was also studied. The results have shown that an electron donating substituent in the position of the nitro group imparts high light resistance to this group of substances.

Multicomponent derivative spectroscopic analysis of sulfamethoxazole and trimethoprim

Abstract Sulfamethoxazole and trimethoprim, frequently combined in chemotherapeutic practice, are analysed by a variety of chromatographic and conventional methods. In this investigation, a multicomponent derivative spectroscopic method was employed. Determination of the two substances in mixtures of varying concentrations was effected by first derivative measurements at 280 and 294 nm. The calibration curves demonstrated correlation coefficients greater than 0.99. Quality control data representing concentrations of artificial mixtures of both components at low and high levels in alternating fashion exhibited coefficients of variation consistently below 3% and sensitivities well below 5 mg 100 ml .

Analytical Study of Nifedipine and Its Photo - Oxidized Form

AbstractNifedipine, a calcium channel blocking dihydrophridine derivative, undergoes ready photochemical conversion to the corresponding pyridine derivative when exposed to normal laboratory and UV light. the Photo-Oxidation of the drug leads to remarkable diminution of pharmacological activity.The study describes a direct and simple spectrophotometric method for the simultaneous determination of both nifedipine and its oxidized degradation product. The molar absorptivities of both components at 237, 280 and 360 nm were also calculated. The method is based on the measurement of absorbance values at two wavelengths and the calculation of the concentrations of the two components in the mixture by solving for two simultaneous equations.

Changes in Glutathione, Glutathione Reductase and Glutathione-S-Transferase as a Function of Cell Concentration and Age

The activities of glutathione-S-transferase (GST) and glutathione reductase (GSR) in mouse lymphocytes as a function of cell concentration and age were determined. Lymphocytes from 2-, 9- and 24-month-old mice were isolated and the activity of GST was determined spectrophotometrically using 1-chloro-2,4-dinitrobenzene as the substrate. Lymphocyte concentrations of 0.44, 0.75 and 0.55 X 10(6) cells/ml were found to be optimal for assaying GST in 2-, 9- and 24-month-old mice, respectively. Determination of GSR activity was based on NADPH reduction of oxidized glutathione and cell concentrations of 0.29, 0.30 and 0.22 X 10(6) cells/ml were chosen for assaying the enzyme activity for the three age groups, respectively. Glutathione levels and GSR activity of mice lymphocytes were higher in 2- and 24-month-old mice as compared to 9-month-old animals. However, GST activity of mouse lymphocytes was low in 2- and 9-month-old mice and increased significantly in 24-month-old animals.

Comparison of pharmacokinetics and pharmacodynamics of a conventional and a new rapidly dissolving glibenclamide preparation

Abstract Glibenclamide is an oral hypoglycemie agent used in the treatment of non-insulin dependent diabetes. It is a weak acid and is poorly soluble in water. In this investigation, the pharmacokinetics and pharmacodynamics of a new rapidly dissolving formula (Oramide) containing only 3.5 mg of the drug was compared with a conventional 5 mg preparation (Daonil). The rate and extent of in vitro dissolution of Oramide was significantly higher than Daonil. Despite the higher amount of the drug in Daonil both preparations exhibited similar plasma glibenclamide concentration-time profiles. Furthermore, the release of insulin and the reduction of plasma glucose levels were not statistically different in both experimental groups. The faster dissolution rate of Oramide formulation has, therefore, rendered it bioequivalent to Daonil which contains a higher amount of active ingredient.

Effect of Ofloxacin on the Pharmacokinetics of a Single Intravenous Theophylline Dose

The effect of ofloxacin taken for 8 days (200 mg twice daily) on the pharmacokinetics of a single intravenous dose of theophylline (4.3 mg/kg over 15 min) was studied in a crossover procedure among seven healthy male volunteers. Theophylline concentrations were measured serially for 10 h by the immunofluorescence polarization technique. No significant effect of ofloxacin was found on theophylline clearance, half-life, or volume of distribution. It is therefore concluded that ofloxacin and theophylline can be safely administered together.

Effect of forskolin on cAMP accumulation and ketogenesis in isolated hepatocytes

The effect of forskolin on ketogenesis and cAMP accumulation was studied in hepatocytes from euthyroid and hypothyroid rats. Forskolin stimulated ketogenesis, cAMP production and potentiated glucagon-stimulated cAMP accumulation on both euthyroid and hypothyroid groups. The ketogenic effect of glucagon was inhibited by forskolin in both groups. Also, forskolin, glucagon and methylisobutylxanthine (MIX) combined did not significantly increase ketogenesis.

Intersubject variability in plasma theophylline levels after oral and intravenous administration in Jordanian patients with chronic obstructive pulmonary disease.

Plasma theophylline concentrations were determined in 151 Jordanian patients with chronic obstructive pulmonary disease. Mean plasma levels after oral administration were below the therapeutic range and significantly lower than after intravenous administration. Plasma levels in patients with congestive heart failure (CHF) were higher than in patients with no CHF. Trough plasma theophylline concentrations after intravenous administration in patients less than 18 years of age were significantly lower than in those aged 18-60 years. The overall results are in agreement with observations made in other ethnic groups.