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Y M el-Sayed

Publications and source records attributed to Y M el-Sayed.

36 records · Page 2Linked to original sources
PubMed1989

Performance of two predictive methods for calculation of the key pharmacokinetic parameters for gentamicin dosage individualization.

Performance of two methods for determination of the apparent volume of distribution (Vd) and the elimination half-life (t1/2) for gentamicin was evaluated in 20 non-obese acutely ill patients. The patients had varying degrees of renal function. Initial creatinine clearance ranged from 22.7-103.1 ml/min, with a mean value (+/- SEM) of 63.26 (+/- 5.74) ml/min, and serum creatinine concentration was 1.37 (+/- 0.13) mg/dl, with a range of 0.70-3.0 mg/dl. The total daily dose of gentamicin ranged from 1.85-4.71 mg/kg. Two different methods were used for Vd calculation: the Hull-Sarubbi method and Chiou midpoint-back-extrapolation method. For t1/2 estimation, the Hull-Sarubbi and Cutler methods were used. These values were compared with the values obtained by the Sawchuk-Zaske method. Mean predicted error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were calculated for each method. Prediction bias and precision were compared statistically between each method by calculating the 95% confidence intervals of the delta MA and delta MAE, respectively. The MAEs revealed that the precision of Vd predictions were within 1.04 litre and 0.62 litre for the Hull-Sarubbi and Chiou methods, respectively. For the elimination half-life, none of the methods performance exhibited substantial bias. The Hull-Sarubbi method, however, was less biased and more precise than the Cutler method.

Adult↗
PubMed1989

Comparison of fluorescence polarization immunoassay and HPLC for the determination of theophylline in serum.

Theophylline in serum was measured by fluorescence polarization immunoassay (FPIA) and by high-performance liquid chromatography (HPLC). Within-run precision studies using control samples in the subtherapeutic, therapeutic and toxic concentrations, resulted in coefficients of variation in the range of 2.86-3.12% (FPIA) and 2.1-3.66% (HPLC), respectively. Between-run precision ranged from 2.76-6.2% for FPIA and from 2.51-6.0% for HPLC. The mean recovery for three spiked controls was 98.9% for FPIA and 98.8% for HPLC. Comparison of 60 patients' samples, assayed with both methods, indicated an extremely good analytical correlation (r = 0.990). The FPIA method displayed a slight but consistent positive bias in relation to the concentration of theophylline present in patients sera. Caffeine was found to exhibit a positive bias to 13%, over a caffeine concentration range of 10-40 micrograms/ml. The HPLC method offers an advantage for measurements of both caffeine and theophylline simultaneously. The FPIA offers significant advantages in speed of analysis and turnover-time, while maintaining accuracy and precision compared with those of established HPLC procedures.

Caffeine↗
PubMed1989

A rapid high-performance liquid chromatography assay of glibenclamide in serum.

A rapid high-performance liquid chromatography (HPLC) determination of glibenclamide in human serum is described. Serum samples to which flufenamic acid has been added as internal standard were treated with acetonitrile as a protein precipitant. After centrifugation, separation and reconstitution, the redissolved residue was eluted from 5 mu Spherisorb C-8 reversed phase column at ambient temperature using a mobile phase consisting of acetonitrile-water (45:55 v/v) at pH 3.7-3.8 and pumped at a flow rate 2 ml/min. The effluent was monitored at 230 nm. The analysis time was no longer than 12 min. A linear relationship between the peak height ratio (glibenclamide/flufenamic acid) and concentration was obtained in the range 20-400 ng/ml. A typical calibration curve has a regression equation y = 0.0035x + 0.015 (r = 0.9999). The detection limit of glibenclamide in serum was 20 ng/ml. The mean recovery of drug from serum samples spiked with known amounts of glibenclamide was 96.77%. Within-day and between-day coefficients of variation were 1.6-4.0% and 1.4-3.5%, respectively. Stability testing indicated that glibenclamide was stable for at least 10 days in serum -20 degrees C. The method developed was applied to determine some pharmacokinetic parameters after the oral administration of 5 mg glibenclamide tablets to a human volunteer.

Administration, Oral↗
PubMed1989

Acetylation phenotyping of isoniazid using a simple and accurate high-performance liquid chromatography.

A simple, specific, accurate and reproducible method for the analysis of isoniazid and its major metabolite, N-acetylisoniazid in urine using high-performance liquid chromatography (HPLC) is described. The assay is performed after extraction of isoniazid, N-acetylisoniazid and 5-(4-methylphenyl)-5-phenylhydantoin (internal standard) from urine using a mixture of chloroform:isopropanol (70:30, v/v) and eluted from a 5 microns C-18 reversed phase column at ambient temperature with a mobile phase consisting of 10 mM sodium acetate:methanol:acetonitrile (40:40:20, v/v) containing 10 mM dioctylsulphosuccinate sodium and adjusted to pH 2.9 with sulphuric acid (less than 1 ml), at a flow rate of 1 ml/min with u.v. detection at 266 nm. Quantification was achieved by the measurement of the peak height ratio, and the absolute recoveries ranged from 94 to 99%. Within-day coefficients of variation ranged from 2.81 to 4.54% for isoniazid and from 2.37 to 3.75% for N-acetylisoniazid. Between-day CVs varied from 3.27 to 5.62% and from 2.5 to 4.91% for isoniazid and N-acetylisoniazid, respectively. Preliminary stability tests using a urine sample from a subject showed an increase in mean isoniazid concentration of about 25% after 1 month storage at -20 degrees C. The method was used for acetylation phenotyping of five individuals.

Acetylation↗
PubMed1989

Comparison of the pharmacokinetics and pharmacodynamics of two commercial products containing glibenclamide.

This investigation was carried out to evaluate the in vitro dissolution as well as the pharmacokinetic and pharmacodynamic properties of two tablet oral dosage forms of glibenclamide, Daonil (product A) and Glucomid (product B). The two products were found to comply with the compendial requirements for both disintegration and content uniformity. Further, the in vitro dissolution characteristics of the two products are similar. The bioavailability and pharmacodynamic studies were carried out on 16 healthy male adult volunteers who received a single dose of each product in a double-blind crossover design. Blood samples were obtained over a 12-h interval and analyzed for serum glucose by glucose-oxidase method, insulin by radioimmunoassay and glibenclamide by a sensitive HPLC assay. The two products were not found to be significantly different with respect to peak serum concentrations (187.9 +/- 13.3 and 167.6 +/- 9.1 ng.ml-1 for A and B, respectively) or to the corresponding peak times (4.2 +/- 0.2 and 4.1 +/- 0.2 h for A and B, respectively). Furthermore, the two products were not found significantly different in the extent of absorption as indicated by the area under serum concentration-time curve (1,118.0 +/- 86.7 and 986.5 +/- 75.1 ng.h.ml-1 for A and B, respectively). The two products were also found to be pharmacodynamically equivalent. This was reflected by the comparable serum glucose and insulin levels. These levels correlated very well with glibenclamide concentrations after the administration of each product. These findings indicate that the two products are bioequivalent in terms of bioavailability and pharmacodynamic effects in normal healthy males.

Adult↗
PubMed1989

Effect of age and renal function on gentamicin pharmacokinetic parameters.

The effect of age and renal function on gentamicin pharmacokinetic parameters were studied in 125 patients with various degrees of renal function. Patients were grouped according to age. Group 1 ranged from 18-40 years (46 patients), group 2 ranged from 41-64 years (53 patients) and group 3 ranged from 65-92 years (26 patients). Elimination rate constant (K) were 0.28 +/- 0.01 h-1 (mean +/- SEM), 0.23 +/- 0.02 h-1, and 0.16 +/- 0.01 h-1 for groups 1, 2 and 3, respectively. Total body clearance (Clt) were 86.21 +/- 5.0 ml/min, 62.41 +/- 4.36 ml/min, and 46.08 +/- 3.89 ml/min, for group 1, 2 and 3, respectively. No significant differences were found between groups with respect to apparent volume of distribution. There was a significant decrease in creatinine clearance (Clcr) with increase in age. Linear regression analysis revealed good correlations between age of the patients and K (r = 0.4132, p less than 0.05), between age and Clt (r = 0.3999, p less than 0.05) and between age and Clcr (r = 0.5241, p less than 0.05). However, poor correlations between age and apparent volume of distribution and between age and serum creatinine concentration were obtained. Significant relationships were also obtained between the composite parameters Clt/age and K/age vs Clcr (r = 0.7064, p less than 0.001, and r = 0.7200, p less than 0.001, respectively). On the other hand, no significant relations were found between K/Clcr and Clt/Clcr vs age of the patients. These findings suggest that the elimination of gentamicin is independent of age of the patient but is highly dependent on renal function.

Adolescent↗
PubMed1989

Phenytoin Michaelis-Menten pharmacokinetics in Saudi patients.

The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 17 epileptic Saudi patients receiving phenytoin. Their ages ranged from 2.5 to 47 years (mean 21 years) and their weight ranged from 9.5 to 80 kg (mean 53 kg). Eight were females and 9 were males. Phenytoin serum concentrations at steady-state were measured using the fluorescence polarization immunoassay. The mean (+/- s.e.m) for Vmax and Km were, respectively, 10.93 +/- 0.78 mg.kg-1.day-1 and 7.75 +/- 0.66 mg.l-1 for children and 6.91 +/- 0.4 mg.kg-1.day-1 and 6.44 +/- 1.01 mg.l-1 for adults. The derived values of Vmax and Km were used to predict the steady-state serum phenytoin concentrations following a change in dose for 7 adult patients. There was a highly significant correlation between observed and predicted steady-state concentrations (r = 0.968, p less than 0.001). Linear regression analysis of Vmax vs age revealed a significant decline in Vmax with age (r = 0.877, p less than 0.01). There is a significant increase in Vmax with weight (r = 0.816, p less than 0.01). A plot of Km vs age and weight showed a poor correlation (r = 0.302, r = 0.218, respectively) and a large amount of variability. Based on this data, the daily phenytoin doses for children and adults are 7.21 mg.kg-1 and 4.83 mg.kg-1, respectively, in order to achieve and maintain a steady-state phenytoin concentration of 15 mg.l-1.

Adolescent↗
PubMed1988

High performance liquid chromatographic analysis of caffeine concentrations in plasma and saliva.

A rapid high performance liquid chromatographic (HPLC) method for the analysis of caffeine in plasma and saliva is described. Samples of saliva and plasma were purified using zinc sulphate solution as protein precipitant. The supernatant was injected directly onto the column. The mobile phase consisted of ammonium acetate buffer:acetonitrile:methanol (82:15:3, v/v). Measurements were carried out at 254 nm. Acetanilide was used as the internal standard and analysis was completed in 10 min. No interference from endogenous components or other methylxanthines was observed. The coefficients of variation for within day and between day analysis for both saliva and plasma were less than 7.66%. Samples were collected from 20 volunteers. The correlation coefficient between plasma and saliva caffeine concentrations was found to be 0.98.

Adult↗
PubMed1988

Correlation between predicted and measured digoxin serum concentrations.

Measurement of digoxin serum concentration can be useful as a direct guide to the dose appropriate to individual patients. Therefore, we have attempted to predict digoxin serum concentration in 62 patients with a wide range of body weight, age and renal function, using creatinine clearance and individual digoxin dose. Creatinine clearance in each patient was determined by the Cockroft and Gault method (1). Digoxin clearance was determined by Scheiner's method (2). Once digoxin clearance was determined, the predicted steady-state serum concentration was calculated using general pharmacokinetic principles. Each patient was on digoxin therapy for at least 1 month. Digoxin serum concentration was measured by the newly developed fluorescence polarization immunoassay (FPIA). A linear regression analysis was performed on the data from the predicted and measured serum level which yielded a slope of 0.9463, intercept of 0.0950 and a correlation coefficient (r) of 0.9600. The method was found to be very useful to predict digoxin serum levels in overdosed and underdosed patients.

Adult↗
PubMed1988

A bioequivalence study of six brands of cephalexin.

The bioequivalence of six brands of cephalexin capsules or tablets was studied in six healthy volunteers in a crossover design. Single oral doses (1 X 500 mg) of each product were administered at intervals of 1 week. Bioequivalence was assessed by a urinary excretion method in which the drug was assayed by a sensitive and precise high pressure liquid chromatographic (HPLC) method. Statistical analysis of the cumulative urinary amounts of cephalexin excreted after 7 h indicated no significant differences between brand A and the other brands. However, brand C was significantly different from brands F and B. The various brands did not differ from each other with respect to urinary excretion rate, time to reach the urinary peak height, elimination rate constant and absorption rate constant. The study demonstrated that the six products of cephalexin were bioequivalent.

Adult↗
PubMed1988

A rapid and sensitive high-performance liquid chromatographic method for the determination of diclofenac sodium in serum and its use in pharmacokinetic studies.

A rapid, and sensitive high-performance liquid chromatographic method has been developed for the determination of diclofenac sodium in serum using flufenamic acid as the internal standard. Serum protein was precipitated with acetonitrile. The drugs were eluted from a 5 microns C-8 reversed-phase column at ambient temperature with a mobile phase consisting of acetonitrile-water (50:50% v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL min-1 with UV detection at 280 nm. Each analysis required no longer than 10 min. Quantitation was achieved by the measurement of the peak-height ratio and the relative and absolute recoveries varied from 90 to 98%. Detection limits for diclofenac sodium in serum is 25 ng mL-1. Intraday coefficients of variation (CV) ranged from 2.47 to 4.61% and interday CVs from 3.52 to 7% at three different concentrations. Preliminary stability tests showed that diclofenac sodium is stable for at least 2 weeks in serum after freezing. The method is applied for the determination of the pharmacokinetic parameters of diclofenac after administration of two formulations (enteric-coated tablet and slow-release tablet), to a healthy male volunteer.

Adult↗
PubMed1987

High performance liquid chromatographic analysis of cephalexin in serum and urine.

A rapid, highly sensitive high performance liquid chromatographic method has been developed for the determination of cephalexin in serum and urine. Serum protein was precipitated with 1% zinc sulphate solution containing cephradine as the internal standard. The drugs were eluted from a 5 micron, C-18 reversed-phase column at ambient temperature with a mobile phase consisting of acetonitrile-methanol-acetate buffer of pH 4.2 (10:10:80%), at a flow rate of 1.4 ml/min with ultraviolet detection at 254 nm. Each analysis lasted 9 min. Quantification was achieved by the measurement of the peak-height ratio and the relative and absolute recoveries varied from 98 to 103%. Detection limits for cephalexin were 1 microgram/ml in serum and 5 micrograms/ml in urine. Within-run coefficient of variation ranged from 0.73 to 5.63% at three different concentrations for the serum and urine assay.

Adult↗
PubMed1986

Comparison of fluorescence polarization immunoassay and high performance liquid chromatography for the quantitative determination of phenytoin, phenobarbitone and carbamazepine in serum.

The Abbott TDx fluorescence polarization immunoassay (FPIA) system has been evaluated and compared with well-established high performance liquid chromatography (HPLC) for the determination of three anticonvulsant drugs: phenytoin, phenobarbitone and carbamazepine. These assays were evaluated for precision, calibration curve stability, specificity and accuracy. Within-run precision studies using control samples (n = 15) in the subtherapeutic, therapeutic, and toxic concentrations, resulted in coefficients of variation in the range of 1.79-3.99% (FPIA) and 1.16-2.52% (HPLC), respectively. Between-run precision ranged from 2.32-6.34% for FPIA and from 2.04-3.38% for HPLC. Comparison of 122 patient samples assayed with both methods indicated an extremely good analytical correlation (r = 0.96) for all three comparisons. The FPIA method offers significant advantages in calibration curve stability while maintaining accuracy and precision comparable with those of established HPLC procedures.

Carbamazepine↗
PubMed1984

Evaluation of the fluorescence polarization immunoassay for quantitation of digoxin in serum.

Digoxin in serum was measured by fluorescence polarization immunoassay (FPIA) and by radioimmunoassay (RIA). Intraday precision of the FPIA method determined by replicate analysis of three controls (low, medium, and high) gave coefficients of variation of 5.41, 2.67, and 2.37%, respectively. The interday coefficients of variation were 5.71, 4.55, and 1.93% for the low, medium, and high controls, respectively. The mean recovery for three spiked controls was 98%. Quantitative results obtained by FPIA on serum samples from patients receiving digoxin were compared with the results obtained by RIA. The correlation coefficient was 0.989. The stability of the standard curve in FPIA was evaluated by recalibrating the instrument at two intervals, 21 days apart, and superimposing the standard curve. No significant changes were found in polarization values.

Digoxin↗
PubMedDate not supplied

Preparation and in-vitro evaluation of sustained-release metoclopramide hydrochloride microspheres.

Sustained-release metoclopramide microspheres were successfully prepared using cellulose propionate polymer at 1:2 drug to polymer ratio employing solvent evaporation technique and using acetone as the polymer solvent. The prepared microspheres at three stirring speeds were characterized with regard to their drug content, particle size distribution, surface topography using SEM and their release profiles at two different pHs at 37 degrees C. The surface of all samples was smooth with very few irregular elevations or depressions. The average particle size decreases as the rotational speed increases and was found to be 1320, 774 and 345 microns at 600, 900 and 1200 rpm, respectively. The average % drug entrapped was found to be 90.5, 100.1 and 60.0% at 600, 900 and 1200 rpm, respectively. Small differences in the release rate were observed due to different rotation speeds with an apparent lower dissolution for batches produced at 1200 rpm probably due to the properties of the coat. The effect of storage under accelerated conditions for 10 weeks on the release characteristics of these microspheres was also studied. The release properties of the microspheres did not change after storing them at 40 degrees C/80% relative humidity for 10 weeks.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Development and in-vitro evaluation of sustained-release meclofenamic acid microspheres.

Meclofenamic acid (MFA) sustained-release microspheres were prepared by the solvent evaporation method using cellulose propionate (CP) polymer and acetone as the polymer solvent. Polyethylene glycol (PEG) was used as a channelling agent to improve the release properties of MFA at 1:2:1 drug to polymer to PEG ratio. The microspheres prepared at three different speeds (600, 800 and 1000 rpm) were characterized with regard to their surface morphology, average drug content, particle size distribution and release profiles in phosphate buffer, pH 8.0 at 37 degrees C. The microspheres were stored under accelerated conditions for 3 months and the effect of storage on the different characteristics was studied. Spherical particles with essentially smooth surface and few residual drug crystals on the surface were formed. Smaller particles were formed at higher agitation speeds. The release rate of MFA from these microspheres was not affected by the molecular weight of CP polymer. PEG 2000 was found to have a more enhancing effect on the rate of the release than PEG 4000. The physical properties of the microspheres and their release characteristics were not altered by storing the product at 40 degrees C/80% relative humidity (R.H.) for 3 months.

Anti-Inflammatory Agents, Non-Steroidal↗