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Biomedical subjects

S I Islam

Publications and source records attributed to S I Islam.

35 records · Page 2Linked to original sources
PubMed1990

Comparison of non-kinetic and kinetic approaches to individualization of gentamicin dosage.

A prospective study was carried out in 40 acutely ill patients to compare the non-kinetic and kinetic approaches to individualization of the dosage regimen of gentamicin. The patients were divided into two equal groups. For the non-kinetic group, the doses were derived from the physician's personal experience, on a mg/kg basis, and by use of nomograms. The total daily dose ranged from 1.43 to 4.5 mg/kg. Based on serum concentration measurements, the dosage regimen for individual patient was calculated by Sawchuk-Zaske's method. The calculated doses were compared to the prescribed doses in each patient. Of the patients on empirically prescribed doses 65% received 36% more drug than the calculated dose and 20% received 36% less than the calculated dose. The calculated dosing intervals were greater than the recommended intervals in 60% of the patients. The gentamicin trough concentration was greater than 2 micrograms/ml in 70% of the patients. There was a significant tendency to overdosage of the patients. For the kinetic group, following administration of the calculated dose, the steady-state peak and trough concentrations in each patient were measured. The correlation of measured to predicted steady-state serum concentrations was excellent (r = 0.9968, p less than 0.05). About 85% of the served trough concentrations and 90% of the peak values fell within the therapeutic range. The mean of the prediction error (ME), mean absolute error (MAE), mean squared error (MSE), and root mean squared error (RMSE) of the trough and peak concentrations were calculated. The 95% confidence interval of the ME for the trough and peak concentrations included zero, which shows that the prediction was not significantly biased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

High-performance liquid chromatographic analysis of theophylline in serum and its use in therapeutic drug monitoring.

A rapid, highly sensitive high-performance liquid chromatographic method has been developed for the determination of theophylline in serum using beta-hydroxyethyltheophylline as an internal standard (IS). Theophylline and IS were extracted from serum using a mixture of dichloromethane: isopropanol (90: 10, v/v) and eluted from a 5 microns, C-18 reversed-phase column at 60 degrees C with a mobile phase consisting of sodium acetate buffer-acetonitrile (90:10, v/v), at a flow rate of 1 ml/min with ultraviolet detection at 280 nm. Each analysis required no longer than 7 min to perform. Quantification was achieved by the measurement of the peak: height ratio and the relative and absolute recoveries varied from 86 to 100%. Within-day coefficients of variation ranged from 2.9 to 5.1% and between-day coefficients of variation from 1.1 to 5.9% in subtherapeutic, therapeutic, and toxic concentrations.

Chromatography, High Pressure Liquid↗
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

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

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

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↗
PubMed1986

Comparison of the fluorescence polarization immunoassay and the microbiological assay methods for the determination of gentamicin concentration in human serum.

The performance of the fluorescence polarization immunoassay (FPIA) was compared with that of a microbiological assay for the measurement of serum gentamicin concentrations. Within-run precision from duplicate assays of two concentrations (4 and 8 micrograms/ml) using FPIA and the microbiological assay yielded coefficients of variation (r) of 2.62%, 1.76% (n = 12) and 8.06%, 6.87% (n = 12), respectively. Day-to-day precision was estimated by repetitive analysis of 4 and 8 micrograms/ml control samples over a 3-week period. Coefficients of variation (r) were 2.57%, 3.09% (n = 8) and 10.71%, 14.20% (n = 8) for FPIA and the microbiological assay, respectively. Linear regression analysis performed on data from parallel determinations on 143 patient samples by the two methods showed correlations in the order of 0.74. The FPIA offers a rapid, efficient, and accurate system for therapeutic monitoring of gentamicin serum levels.

Biological Assay↗
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↗
PubMed1983

Inhibition of lipid peroxide decomposition by compounds which bind with cytochrome p-450.

The kinetics of lipid peroxide decomposition catalysed by microsomal enzymes and inhibited by SKF-525 A, hexobarbital, phenobarbital and aniline were investigated. The results indicate that the in vitro interaction of hexobarbital and SKF-525 A (type I binding compounds) with microsomal cytochrome p-450 inhibits the peroxidase activity while the in vitro interaction of aniline (type II binding compound) only slightly affect the peroxidase activity. It is suggested that LAHPO and type I binding compounds are competing for the hydrophobic binding site on cytochrome p-450, while type II binding compounds such as aniline negate electron transfer non-competitively by combining with the heme.

Aniline Compounds↗
PubMed1982

Polymorphic acetylation of sulphamethazine in rural bedouin and urban-dwellers in Saudi Arabia.

1. The polymorphic acetylation of sulphamethazine (sulphadimidine, sulphamezathine) has been investigated in a population of 109 Saudi male arabs of rural bedouin origin and in 126 Saudi female arabs from urban cosmopolitan areas of Jeddah. 2. Rural males excreted 5-79% of the administered dose (1 X 5 g/m2 body surface area) in the 0-12 h urine and the urban females excreted 5-97%. 3. The frequency distribution of the ratio acetyl sulphamethazine/sulphamethazine was bimodal in rural, urban and the combined populations with a clear antimode at 70% acetylation of the recovered dose. 4. The incidence of slow acetylators was 67 X 9, 59 X 5 and 63 X 4% in the rural, urban and combined populations. The incidence of the As allele in Saudi arabs was thus 0 X 80+/-0 X 03 S.E.M., which is similar to that found in the neighbouring countries, of Egypt and Sudan. Since no significant difference in As frequency was apparent between the rural (pure) and urban (cosmopolitan) arabs, it is concluded that immigrants to Saudi Arabia from other muslim countries have not affected the gene frequencies with respect to acetylation. 5. Methodology of assessing acetylation phenotype is discussed. It would appear that urine analysis alone gives satisfactory discrimination between phenotypes.

Acetylation↗
PubMed1980

The polymorphic 4-hydroxylation of debrisoquine in a Saudi arab population.

1. Debrisoquine 4-hydroxylation was polymorphic in 102 Saudi arab volunteers, the population comprising one phenotypically poor metabolizer and 101 phenotypically extensive metabolizers of debrisoquine. 2. Mean urinary recoveries of drug and metabolite were low in Saudis (15 +/- 10% dose, mean +/- S.D.), which compared well with previously studied populations of Egyptians (16%) and Ghanaians (18%), but which were lower than those seen in a UK white population (41%). 3. Saudis, like Egyptians, were more extensive metabolizers of debrisoquine than UK whites, as judged by the metabolic ratio (% dose as debrisoquine/% dose as 4-hydroxy-debrisoquine eliminated in the urine). 4. Neither sex, urine collection period nor urinary recovery of drug and metabolite had any statistically significant effect upon the distribution of metabolic ratios in Saudis. 5. The frequency of the DL allele controlling the recessive poor metabolizer trait was 0.099 +/- 0.049 (+/- S.E.M.) in Saudis, which compared well to Egyptians (0.118 +/- 0.059) but was significantly lower than that for UK whites (0.298 +/- 0.030). 6. These findings raise questions regarding the efficacy and safety in Saudis of drugs undergoing oxidative metabolism which have been evaluated for usage in European white subjects.

Adolescent↗
PubMed1975

A comparative study of the effect of some steroid hormones on the response of rats to other drugs.

The effect of a series of steroid hormones on the pentetrazol convulsing action, hexobarbital narcotic action and hepatic drug metabolizing enzyme activities was determined in rats. All steroid compounds used antagonized the pentetrazol effect: the most potent was cortisone and the least potent testosterone. Glucocorticoids and androgens shortened the hexobarbital sleeping time and increased the hepatic drug metabolizing enzyme activity. Estradiol exhibited the opposite effect, whereas progesterone and desoxycorticosterone did not affect these two parameters.

Adrenal Cortex Hormones↗