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S J Soldin

Publications and source records attributed to S J Soldin.

At least 73 records · Page 4Linked to original sources
PubMed1991

A preliminary study to evaluate an in vitro assay for determining patient whole blood immunosuppressive cyclosporine A and metabolite activity: comparison with cytosolic binding assays using cyclophilin or a 50-kilodalton binding protein, and the Abbott TDx cyclosporine A parent, and parent and metabolites assays.

Thirty-five allograft recipients undergoing cyclosporine A (CsA) therapy were randomly selected to evaluate a "novel" in vitro assay that determines CsA and metabolite immunosuppressive activity in whole blood. The assay uses a third party mixed lymphocyte culture (MLC) system to which patient whole blood extracts containing CsA and metabolites are added. The ability of the extracted CsA and metabolites to inhibit proliferation in this system is proportional to the immune suppressive activity in whole blood. Comparison of the MLC suppression assay against Abbott TDx parent, TDx parent and metabolites, and radioreceptor assays utilizing cyclophilin or a 50-kDa binding protein isolated from JURKAT cytosol gave the following correlation coefficients: r = 0.612, r = 0.672, r = 0.362, and r = 0.775, respectively.

Amino Acid Isomerases↗
PubMed1990

A dry-strip immunometric assay for digoxin on the Ames Seralyzer.

We evaluated the Ames Seralyzer III with a new reagent and drystrip test for assay of digoxin. Assay precision was acceptable in the therapeutic range. Within-run imprecision (coefficient of variation, n = 20) was 7% at 0.9 ng/ml (1.2 nM) and 3.5% at 1.9 ng/ml (2.4 nM); run-to-run imprecision was 7.6% at 0.8 ng/ml (1.0 nM) and 5.7% at 2.1 ng/ml (2.7 nM). The method is very reproducible and is linear between 0.5 and 4.3 ng/ml (0.6-5.5 nM). The assay performed well with patient samples, with Abbott TDx used as the reference procedure. Bilirubin up to 16 mg/dl (273 microM) and hemoglobin up to 11 g/l do not cause interference. Digoxin-like immunoreactive factors cause minimal interference. Some digoxin metabolites such as monodigitoxoside, bis-digitoxoside, and digoxigenin cross-react with the digoxin antibody. Patients on spironolactone have falsely increased digoxin values. The new digoxin assay is easy to perform and uses 30 microliters serum; the result can be reported in 15-20 min.

Antibody Specificity↗
PubMed1989

Disposition of oral methotrexate in children with acute lymphoblastic leukemia and its relation to 6-mercaptopurine pharmacokinetics.

We studied the disposition pharmacokinetics of methotrexate (MTX) given orally to 16 children with acute lymphoblastic leukemia (ALL) and its relation to the pharmacokinetics of 6-mercaptopurine (6MP) in the same children. There was an eightfold variability in area-under-concentration time-curve (AUC) of MTX achieved by the same dose. Excellent correlation existed between peak concentrations and AUC0----infinity (r = 0.95, P less than 0.001). Elimination T1/2 was between 1.34 and 5 hours (mean 2.16 +/- 0.23 hr, mean +/- SE). A weak correlation existed between AUC achieved by 1 mg/m2 MTX and patients' age or body weight. Weak but significant correlation existed between AUC achieved by 1 mg/m2 of MTX vs. 6MP (r = 0.54, P less than 0.05). In 13/16 patients peak concentrations were achieved at 60 minutes. There was a significantly larger AUC of 6MP achieved by a standardized dose in longer therapy (greater than 15 mo) vs. short therapy (less than 12 mo) (462 +/- 75 and 246 +/- 58 ng.ml-1.min.mg-1.m2, P less than 0.025). No statistical differences in AUC of MTX were found between short and long therapy. The large interpatient variability in MTX pharmacokinetics supports the possibility that differences in absorption and/or clearance of the drug may affect the clinical response. Because of the excellent correlation between peak and AUC of MTX, and because 3 measurements, at 30, 60, and 90 minutes will almost invariably identify the peak, this measurement can be used to estimate AUC for purpose of correlation with clinical outcome.

Administration, Oral↗
PubMed1989

An evaluation of the Kodak Ektachem clinical chemistry slide for theophylline.

We evaluated the Kodak Ektachem clinical chemistry slide for assay of theophylline. Assay precision and accuracy were acceptable in the therapeutic range although precision was poor at low levels of theophylline. The assay performed well with patients' samples using the Abbott TDx as the reference procedure but, as indicated by the manufacturer, uremic samples gave a positive bias, particularly in the therapeutic range. Finally, the significant bias observed with Quality Control material, probably due to matrix sensitivity, is a possible drawback.

Humans↗
PubMed1989

A rapid, reliable high-performance liquid chromatographic micromethod for the measurement of cyclosporine in whole blood.

The initiation of a liver transplant program in a pediatric hospital prompted the development of a high-performance liquid chromatography method for monitoring cyclosporine, which requires minimal amounts of blood and produces fast, reliable results. A protein-free filtrate is prepared by mixing 250 microliters of whole blood with 750 microliters of organic solvent (acetonitrile and methanol in the ratio of 9:1) containing the internal standard cyclosporine D. After centrifugation the supernatant is subjected to a quick clean-up using two types of disposable cartridges (C18 and silica Bond Elut), and the eluate is dried, reconstituted in equal parts of acetonitrile and water, and subjected to a final heptane wash to remove late eluting peaks. Chromatography is performed at 75 degrees C using a supelcosil C18 column (15 cm X 4.6 mm) with 3 microns packing and a mobile phase of 77/23 of acetonitrile/phosphate buffer at pH 2.5. Flow rate is 0.6 ml/min, providing a chromatography time of 10 min. Absorbance is measured at 214 nm at a sensitivity setting of 0.01 absorbance units full scale. Recovery for cyclosporine A is between 92 and 104%, and the lower level of sensitivity is 15 micrograms/L. Between-day precision provided coefficient of variation values less than 5% for a control serum of 150 micrograms/L. The method is linear to 3,000 micrograms/L. No interfering substances have been found. The method has proved to be consistent, reliable, and simple enough to be performed by all staff members. Column life for a system used daily is at least 3 months.

Chromatography, High Pressure Liquid↗
PubMed1989

A radioreceptor assay for the measurement of cyclosporine activity: a preliminary report.

Cyclosporine A (CsA) is extensively metabolized in the liver. Some of the known metabolites share immunosuppressive properties with the parent drug. Furthermore, CsA therapy is used in an increasing number of clinical conditions, some of which affect the pharmacokinetics of the drug. At this time, it is not yet known if CsA or its metabolites are responsible for the nephrotoxicity or hepatotoxicity observed in some individuals. Some high-performance liquid chromatography (HPLC) and monoclonal immunoassay procedures measure parent drug and not the pharmacologically active metabolites, while polyclonal immunoassays and nonspecific monoclonal antibody immunoassays measure both parent drug and metabolites. However, it is unlikely that the degree of cross-reactivity with metabolites correlates with their immunosuppressive effect. To overcome these drawbacks, we have developed a method of measuring CsA activity in whole blood using specific receptors from the cytosol of human mononuclear leukocytes that have been semipurified through ultracentrifugation. The basis of the procedure is the competitive binding at specific receptor(s) between a constant concentration of [3H]dihydrocyclosporine and the variable concentrations of cyclosporine and its pharmacologically active metabolites in whole blood. Comparisons between six different assays (three specific, two nonspecific, and the receptor assay) were made. Overall, the two specific radioimmunoassay procedures correlated well to HPLC, while correlation of the two nonspecific immunoassay procedures to HPLC was poor. Poor correlation was also found to exist between the radioreceptor assay and the nonspecific assays, indicating that the cytosolic binding of CsA and its metabolites cannot be correlated to currently available assays.

Antibodies, Monoclonal↗
PubMed1989

An update on digoxin.

This review deals briefly with recent developments in the therapeutic drug monitoring of digoxin. Strategies for decreasing the interference by digoxin metabolites, digoxin-like factors, and spironolactone metabolites in immunoassays of digoxin are discussed. Other issues addressed include the development of alternative methods of analysis, such as receptor assays and "high-pressure" liquid chromatography; digoxin-like factors in hypertension; drug-drug interactions; redistribution of digoxin stores in the body; and forensic considerations.

Digoxin↗
PubMed1989

High-versus low-dose, frequently administered, nebulized albuterol in children with severe, acute asthma.

Thirty-two 5- to 17-year-old children who had severe, acute asthma were randomly assigned to receive either high doses (0.15 mg/kg of body weight per dose) or low doses (0.05 mg/kg of body weight per dose) of nebulized albuterol every 20 minutes for six doses. Compared with the low-dose regimen, the high-dose regimen resulted in significantly greater improvement in forced expiratory volume in 1 second, forced vital capacity, and wheeze score and a lower hospitalization rate. The changes in heart rate, respiratory rate, blood pressure, white blood cell count, and serum potassium concentration did not differ significantly between the groups. The incidence of side effects, which included tremor, hyperactivity, and vomiting, was not significantly different in the two populations. Serum albuterol levels varied widely, but there was no correlation between the levels and the increase in heart rate or other side effects. high-dose, frequently administered, nebulized albuterol appears both safe and effective in treating severe, acute asthma in children.

Acute Disease↗
PubMed1988

Rapid development of enhanced clearance after high-dose cyclophosphamide.

We have studied the disposition of cyclophosphamide, its major cytotoxic metabolite phosphoramide mustard, and the synthetic glucocorticoid dexamethasone in nine patients receiving high-dose cyclophosphamide daily for 2 days before bone marrow transplantation. The total body clearance of cyclophosphamide was observed to increase from 93 +/- 27 ml/min on the first day to 178 +/- 83 ml/min on the second day. This was associated with an increase in the clearance of dexamethasone from 369 +/- 104 ml/min to 526 +/- 123 ml/min. An increased rate of formation of phosphoramide mustard with higher peak concentrations was also seen. Simulation studies show that these changes are most likely the result of an increase in the hepatic metabolism of cyclophosphamide. These results show that high-dose cyclophosphamide causes an increase in its own clearance and that of dexamethasone through an apparent induction of hepatic-metabolizing enzymes detectable 24 hours after initial exposure to cyclophosphamide.

Adult↗
PubMed1988

Improved receptor assay for measuring digoxin activity.

We describe a receptor assay of digoxin activity involving Na+/K+-ATPase (EC 3.6.1.37) derived from human heart tissue. The procedure requires 500 microL of serum or plasma and incorporates one purification step, with Sep-Pak C18 cartridges (Waters). The method appears to be considerably more specific for digoxin and its cardio-active metabolites than are conventional immunoassays. Cardio-inactive metabolites and several digoxin-like factors cross react only slightly. The between-day coefficient of variation for the procedure ranged from 8.10% to 1.37% for digoxin concentrations between 0.5 and 5.0 nmol/L.

Animals↗
PubMed1988

Disposition of cyclophosphamide on two consecutive cycles of treatment in patients with ovarian carcinoma.

The disposition of cyclophosphamide was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, doxorubicin (adriamycin) 50 mg/m2 and cisplatin 50 mg/m2 during their first and second courses of therapy. Plasma samples were obtained over 24 h following the completion of the cyclophosphamide infusion and assayed for cyclophosphamide by high performance liquid chromatography. The mean disposition of cyclophosphamide conformed to a 2-compartment model with a mean terminal half-life of 7.14 h on the first course and 8.77 h on the second course. Mean area under the plasma concentration versus time curve appeared to increase from 248.8 mg.h/l for the initial course to 282.2 mg.h/l on the second. Mean total body clearance was 2.01 l/h/m2 on the first course and 1.77 l/h/m2 on the second. Volume of distribution on the first and second courses were 15.3 l/m2 and 18.1 l/m2, respectively. These results suggested that cyclophosphamide clearance decreased when given in a bolus fashion every 3 weeks. However, inter-patient and intra-patient variability was large and the differences in the calculated parameters were not statistically significant when the individual patient data was considered. It is concluded that: 1. cyclophosphamide disposition can best be fit by a bi-exponential equation; 2. considerable intra- and interpatient variability in the concentration-time profile will be encountered; 3. cyclophosphamide disposition does not change from the first to the second course. Reasons for the wide variation are proposed.

Adult↗
PubMed1988

Improved liquid chromatographic/immunoassay of digoxin in serum.

This HPLC/immunoassay procedure measures digoxin in serum with no interference from digoxin metabolites or digoxin-like factors. We used solid-phase (C18 and Diol) extraction, a C18 column with a tetrahydrofuran/water mobile phase, and final quantification by fluorescence polarization immunoassay. Deslanoside and gitoxigenin were used as the internal standard and the retention-time marker, respectively. The average CV for 300-microL samples at digoxin concentrations between 0.9 and 3.9 nmol/L was 9.3%. Minimum column lifetime with daily use was three months. We also compared results, for 49 samples from patients taking digoxin, obtained with the Abbott "TDx FPIA digoxin I" and the present procedure. Discrepancies between the two methods were substantial for 20% of the samples.

Chromatography, High Pressure Liquid↗
PubMed1988

Liquid-chromatographic measurement of p-aminobenzoic acid and its metabolites in serum.

This is a high-performance liquid-chromatographic method for measuring p-aminobenzoic acid (PABA) and its metabolites in plasma or serum. Samples are deproteinized, then extracted with organic solvents before chromatography. For quantification, the peak height of the individual compound is compared with that of the internal standard. Analytical recoveries ranged from 41% to 100%, depending on the compound studied. Comparison of patients' samples after oral administration of either N-benzoyl-L-tyrosyl-p-aminobenzoic acid or free PABA revealed that PABA is extensively metabolized and conjugated to either p-acetamidobenzoic acid, p-aminohippuric acid, or p-acetamidohippuric acid. PABA concentrations in serum as measured with the Bratton-Marshall ultraviolet spectrophotometric procedure would appear predominantly to reflect measurements of metabolites, with only a minor contribution from PABA itself.

4-Aminobenzoic Acid↗
PubMed1987

Analysis of salbutamol enantiomers in human urine by chiral high-performance liquid chromatography and preliminary studies related to the stereoselective disposition kinetics in man.

Enantiomers of salbutamol, extracted from human urine, were successfully separated and quantitated by high-performance liquid chromatography with electrochemical detection. This direct resolution was accomplished using a chiral alpha 1-acid glycoprotein column (EnantioPac) maintained at 0 degrees C and a mobile phase consisting of a 0.1% (v/v) triethylamine in 5.3 mM citrate buffer, pH 7.2. An amperometric detector incorporating a glassy carbon electrode was employed for detection. The between-day coefficients of variation for the determination of R(-)- and S(+)-salbutamol in human urine were 4.1 and 4.7%, respectively, at a drug level of 1.0 microgram/ml. The urinary excretion ratio of the biologically active (-)-isomer to (+)-isomer in one healthy subject who received an intravenous dose of racemic salbutamol (1.0 mg) decreased continuously over a 12-h period. A similar excretion pattern exhibiting a far more extensive distortion in the enantiomeric ratio was found in three subjects dosed with a single 4-mg tablet of racemic salbutamol.

Adult↗