摘要:

Ethosuximide (ESM) was determined by the EMIT technique in tears, saliva, cerebrospinal fluid (CSF), and plasma of epileptic subjects. CSF/ plasma, saliva/plasma and saliva/CSF ratios were in good agreement with gasliquid chromatography (GLC). The tears/plasma ratio was not significantly different from the saliva/plasma ratio, although the standard deviation was higher in the latter. These data indicate that ESM can be determined in a quantitatively similar manner in both saliva and tears by EMIT.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The Koup et al. and Chiou et al. clearance estimation methods were evaluated in 19 chronic obstructive pulmonary disease (COPD)/asthmatic patients who were receiving aminophylline by continuous infusion. Estimated theophylline clearance (Clest) was determined using two serum concentrations obtained during the first few hours of therapy (1–16 hr) prior to achievement of steady state. Actual theophylline clearance (Clact) was determined after steady state conditions had been achieved (defined as 4–5 half-lives at the same infusion rate). The correlation between ClactandClestwas highly significant for both the Koup et al. and Chiou et al. methods, r = 0.865, p < 0.001, and r = 0.858, p < 0.001, respectively. The clearance estimation methods were compared with the Food and Drug Administration (FDA) dosage guidelines and shown to be clearly superior in predicting therapeutic steady state theophylline concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Eight subjects were studied in a randomized crossover design to determine the effect of aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), and aluminum hydroxide-magnesium trisilicate (AHMT) on the bioavailability of a single, 600-mg dose of phenytoin administered orally. Each subject received phenytoin alone on two separate occasions and phenytoin plus each of the three antacids on three other occasions. Each antacid was administered as 160 mEq at 1 and 3 hr after each meal and at bedtime on the day phenytoin was given. The mean area under the curve (AUC) was significantly decreased by AMH (p < 0.005) and CC (p < 0.05). AHMT had a similar trend but did not reach statistical significance (p = 0.1). Large inter and intrasubject variability in AUC was observed when phenytoin was administered alone. In two subjects, cumulative urinary 5-(4-hydroxyphenyI)-5-phenylhydantoin at 72 hr (HPPH72) was determined. The amount of HPPH recovered had similar trends as the AUC with antacid treatments but not the same magnitude. In this study, antacids altered not only the extent of absorption but also appeared to alter the rate of absorption. Antacids administered in a peptic ulcer regimen may decrease the AUC of a single dose of phenytoin. Patients should be cautioned against concomitant use of antacids and phenytoin.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

EEG (power spectral analysis) and behavioral effects of single, 5 to 20 mg doses of SAS 643, a newly developed benzodiazepine, were defined in normal male volunteers in relation to drug plasma concentration. A single 20 mg dose of SAS 643 induced an increment in power of fast frequency components (above 16.5 Hz), predominant on posterior leads, and paralleled by a decrement in the 4.5–8 Hz power. A concomitant increase in 0.5–4 Hz power and decrease in 8.5–12 Hz power were also evident in anterior scalp areas. EEG effects were less systematic following the administration of 10 mg, and only occasional at the 5 mg dose. These EEG modifications are qualitatively consistent with the profile of antianxiety compounds, relative to dose and their ongoing time parallels SAS 643 plasma concentration, though the EEG/plasma level correlation was not statistically significant across subjects, due to individual variability. Systematic effects were not observed in any of the behavioral or neuropsychological variables considered. SAS 643 bioavailability and action at the central nervous system (CNS) level is established. The results exemplify the routine applicability of pharmaco-EEG procedures. The topographic differences in SAS 643 EEG effects warrant systematic studies on the issue.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

A method using gas-liquid chromatography-electron-capture detection method is described for rapid, accurate determination of SAS 643 in plasma and urine. The drug is extracted from biological fluid with benzene and converted to the O, O'-bistrimethylsilyl derivative with bis(trimethylsilyl) trifluoroacetamide. The glucuronide form of the drug is extracted after hydrolysis with β-glucuronidase. Nimetazepam is used as internal standard. Moreover, some metabolites such as glucuronide and the N-1-dealkylated and N-1-yl-acetic products are identified. All compounds were confirmed by thinlayer chromatography, mass spectroscopy, and gas-liquid chromatography-mass spectroscopy by comparison with reference products.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Quinidine, an antiarrhythmic drug, was quantitated in serum by a commercially supplied enzyme immunoassay procedure (EMIT®). Replicate analyses of serum controls resulted in a within-assay coefficient of variation of ≤10% and a between-assay coefficient of variation of ≤7%. Patient quinidine results by enzyme immunoassay were compared to those obtained by a nonselective (protein precipitation) and a selective (solvent back-extraction) fluorometric method. Assay selectivity for quinidine versus other drugs and versus the 3-hydroxy metabolite of quinidine was determined. Clinical evaluation of the results indicates the enzyme immunoassay technique to be sensitive for quinidine and more selective than commonly used fluorometric methods relying on back-extraction or protein precipitation.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We have adapted the Syva Emit® gentamicin and tobramycin procedure to the IL microcentrifugal analyzer, MCA III®. With this instrument the recommended instructions for reagent preparation and reaction sequence did not produce a useable standard curve. We modified the dilutions and volumes for the working reagents and reversed the sequence of addition of the working reagents. We assessed the linearity and precision of the analysis and compared the Syva gentamicin and tobramycin Emit procedure on the IL MCA III with the semiautomated procedure on a Gilford Stasar III spectrophotometer. With the IL MCA III® only 3 to 5μ of serum is used, 17 analyses can be obtained in 8 min, and the reagent costs are reduced considerably.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

A sensitive method for monitoring serum or plasma labetalol (2-hydroxy- 5− [1− hydroxy- 2− (1− methyl- 3− phenylpropylamino) ethyl] benzamide hydrochloride) is described. The method is designed to study single dose kinetics and assess predose labetalol levels during chronic treatment. The applicable range of the assay is 10 to 400 ng/ml using 1 ml of plasma or serum. The method uses reverse-phase high pressure liquid chromatography (HPLC), a mobile phase of acetonitrile/pH 3.0 phosphate, and ultraviolet detection at 207 nm. The percentage recovery of labetalol and internal standard (propericiazine) (3-cyano-10-[3–4-hydroxypiperidino) propyl] phenothiazine from serum was 95.6% and 75.5%, respectively. The precision of the method at labetalol serum concentrations of 400 and 50 ng/ml was indicated by a coefficient of variation of 4.3% and 6.9%, respectively. An approximate fourfold variation in plasma labetalol concentration, with plasma levels ranging from 20 to 93 ng/ml, was seen 10 to 11 hours after a dose in a group of patients taking 200 mg twice daily.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The object of a liquid-chromatographic analysis is to separate, identify, and quantitate the constituents of interest in a sample mixture within an acceptable analysis time. This will be achieved by a systematic analysis development rather than by a trial-and-error approach. Such a systematic procedure requires a knowledge of the chromatographic parameters governing resolution and analysis time and their relative influences on resolution and its experimental implication. Furthermore, basic information about the mechanisms of the modes of liquid chromatography (adsorption, partition, ion exchange, and steric exclusion) and about the types of sample which can be preferentially analyzed by them is necessary. This information leads to a rational selection of the separation system that promises the best chance of success. In the subsequent experimental work, the analyst systematically measures and calculates resolution and analysis time as functions of selectivity, capacity, and efficiency of the phase system under selected chromatographic conditions. The essential chromatograms, tables, and graphs resulting from this systematic method of development are documented so that it is possible to replicate the analysis procedure in the laboratories involved. The result is a set of chromatographic conditions capable of achieving an optimum compromise between resolution and analysis time. The procedure is applied to routine therapeutic drug monitoring of antiepileptic drugs in patient serum.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Specific antiepileptic drug (AED) concentrations in serum are believed to cause therapeutic effects in individual patients. Communication between the clinician and the laboratory performing the drug level determinations is therefore essential for safe and effective medication. The now common practice of multiple drug therapy preferably requires simultaneous separation and quantitation of the various drugs and their metabolites. The advantages and disadvantages of current AED analysis methods are discussed. Liquid chromatography (LC) was found to be the most versatile technique for routine and research analysis and can be applied to the determination of common, less common and new AED and metabolites. Carbamazepine and its metabolite, carbamazepine-10,11-epoxide, were determined with high accuracy. The sample preparation procedures, the internal standards, and mode of LC separation used for the analysis are given. The chromatographic parameters for optimized resolution and analysis time of eight AEDs and metabolites were devised with special consideration for the influence of the oven temperature on resolution. About 300 patient serum samples were analyzed by automatic unattended operation. By this method some 50 samples per day can be extracted and analysed. Quantitative results achieved by LC and gas liquid chromatography (GLC) on the same patient samples are reported and chromatograms discussed. Peak scanning was used to demonstrate the presence of compounds which could eventually interfere with the detection of phenylethylmalonamide. The overall accuracy of the employed LC method, the repeatability of retention times on three different columns, and the measured ranges of AED concentrations are reported.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID