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Biomedical subjects

M Zell

Publications and source records attributed to M Zell.

29 records · Page 2Linked to original sources
PubMed1986

Highly sensitive assay of benzodiazepine antagonist in plasma by capillary gas chromatography with nitrogen-selective detection.

A selective and highly sensitive capillary gas chromatographic method was developed for the determination of a benzodiazepine antagonist in human plasma. The analytical procedure involved extraction of the compound and its internal standard from basified plasma with n-butyl chloride-dichloromethane and chromatography of the extract on a DB-5 fused-silica column (30 m X 0.25 mm I.D.), applying automated splitless injection and nitrogen- phosphorus detection. The limit of quantification was about 50 pg/ml, using a 1-ml plasma specimen. The mean inter-assay precision was 2.6% in the concentration range 0.5-10 ng/ml. The method was shown to be specific with respect to various benzodiazepines and their main metabolites. The practicability of the method was demonstrated by the analysis of more than 300 plasma samples from a dose proportionality study performed with human volunteers. Owing to its high sensitivity, the new method can be used to obtain pharmacokinetic parameters of the benzodiazepine antagonist in man after doses near the envisaged therapeutic intravenous dose of less than 1 mg.

Anti-Anxiety Agents↗
PubMed1986

Accuracy of 11 methods for predicting theophylline dose.

Eleven methods for pharmacokinetic determination of theophylline dose were compared, based on the ability of each method to predict theophylline serum concentration and clearance for adults with asthma. Predictions by each method were compared with actual serum theophylline concentrations before and after an aminophylline loading dose was administered to treat bronchospasm in 22 patients. Follow-up serum theophylline concentrations were obtained after maintenance therapy with i.v. aminophylline in 6 patients and an oral sustained-release theophylline product (Theo-Dur, Key) in 16 patients; maintenance doses administered to the patients were calculated by the method of Chiou et al. Two variations of the method of Chiou et al., seven Bayesian methods using one or more measured serum theophylline concentrations, FDA's standardized clearance estimate, and a population-based clearance-estimation method were compared. A one-compartment, open model with first-order elimination was assumed for all calculations. All 11 methods predicted steady-state concentration with minimal bias and good precision. The Chiou and Bayesian methods performed similarly, with the highest precision found for the Bayesian method that incorporated four measured concentrations. The population-based method had the highest correlation coefficient and the lowest mean error for predicting steady-state concentration. Decreasing the number of measured concentrations had a minimal effect on the various Bayesian methods. All methods evaluated are sufficiently accurate for clinical application in patients with stable, uncomplicated asthma.

Acute Disease↗
PubMed1985

Volume of distribution of theophylline in acute exacerbations of reversible airway disease. Effect of body weight.

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.

Adolescent↗
PubMed1983

Determination of the benzodiazepine antagonist Ro 15-1788 in plasma by high-performance liquid chromatography with UV detection.

A sensitive and specific HPLC-assay was developed for the determination of the benzodiazepine antagonist ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a] [1,4]benzodiazepine-3-carboxylate (Ro 15-1788; envisaged INN: flumazepil) in plasma. Ro 15-1788 and the internal standard were extracted from plasma at a basic pH, separated from coextracted plasma components on a reversed-phase column and quantitated by means of a UV detector. Ro 15-1788 was extracted quantitatively from plasma in the concentration range 25.6 to 300 ng/ml. The sensitivity limit was about 10 ng/ml plasma using a 1-ml specimen. The method was shown to be specific with respect to several benzodiazepines and their main metabolites. The method was successfully applied to pharmacokinetic studies in man after oral and intravenous administration of Ro 15-1788.

Benzodiazepinones↗
PubMed1982

Sensitive gas-liquid chromatographic method for the determination of oxiconazole in plasma.

A specific and highly sensitive gas-liquid chromatographic method was developed for the determination of oxiconazole in rat, dog, and human plasma. The compound and its internal standard were extracted from plasma at basic pH with n-hexane-isoamyl alcohol (98:2, v/v), gas chromatographed on 3% SP-2250/Supelcoport (80-100 mesh) and quantified by means of an electron-capture detector. Oxiconazole was extracted almost quantitatively from plasma in the concentration range 10-5000 ng/ml. The sensitivity limit was about 1 ng/ml, using a 1-ml specimen. The method was applied to 13-week tolerance studies in dogs and rats in order to follow oxiconazole concentrations in plasma after oral administration of the compound. The assay was sensitive enough to measure precisely the small amounts of unchanged compound in plasma after intravaginal application of labelled oxiconazole to human volunteers.

Administration, Topical↗
PubMed1980

Baseline studies of the global pollution. I. Occurrence of organohalogens in pristine European and antarctic aquatic environments.

Pristine Alpian fresh water lakes with no run off were selected to monitor the atmospheric fall-out of C6--C12 -organochlorine compounds. Off-shore marine areas were taken for monitoring the average marine pollution by these compounds. In both cases fishes have been used as bioextractors. The analytical work-up combines solvent-partition, liquid chromatography and glass capillary gas chromatography with the electron capture detector. The idenfification is done by matching high-resilution retention indices of unknowns with those of reference compounds. The following compounds could be identified in the spawn of arctic chars (Salvelinus alpinus) caught in off-road Alpian lakes as well as in the liver of predatory antarctic cod (Dissostichus eleginoides) caught near South Georgia, as well as in Peru fish oil and crude sperm oil: hexachlorobenzene alpha-, beta-, gamma-hexachlorocyclohexane; 4,4'-DDT; 4,4'-DDE; 4,4'-DDD; 2,4'-DDE; 2,4'-DDD; heptachloroepoxide; polychlorobiphenyls (PCB) and polychlorocamphenes. Concentrations are given in nanogram/gram total lipid extract (ppb). First value Salvelinus (Alps), second value Dissostich (Antarctic Ocean), alpha-HCH: 40/0,1; beta-HCH: 4,1/0,1; gamma-HCH: 17,2/0,1; HCB: 65/8; 4,4'-DDT: 59/4; 4,4'-DDE: 477/5; sigma DDT 646/11,4; sigma PCB: 1030/32; sigma PCC: 124/68.

Air Pollutants↗
PubMedDate not supplied

Piperidine renin inhibitors: from leads to drug candidates.

Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes. In addition, 14 normalizes albuminuria and kidney tissue damage in these rats when given over a period of 4 weeks. These data suggest that treatment of chronic renal failure patients with a renin inhibitor might result in a significant improvement of the disease status.

Animals↗