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Biomedical subjects

S H Curry

Publications and source records attributed to S H Curry.

At least 73 records · Page 4Linked to original sources
PubMed1982

Clinical effects and metabolism of diazepam in patients with chronic liver disease.

1. After a fixed weight-related dose given intravenously, plasma diazepam concentrations were significantly lower in 11 cirrhotic patients than in controls matched for age and sex, in the 4 h after diazepam administration but not thereafter. 2. When measured at a single fixed time point, a greater proportion of the drug was in the unbound from in the plasma of cirrhotic patients, but non-bound diazepam concentrations were not significantly different in the two groups. 3. Several psychomotor tests showed that cirrhotic patients, although having significantly impaired liver function, did not as a group have increased sensitivity to diazepam compared with their matched controls. 4. Only those cirrhotic patients who at the time of drug administration had impaired cerebral function, as judged by baseline performance of psychomotor tests, showed increased sensitivity to the effects of intravenous diazepam. 5. Psychomotor tests, particularly the Reitan trail test, seem more useful than tests of liver function or drug metabolism for identifying those patients with liver cirrhosis at risk of excessive sedation after diazepam administration.

Adult↗
PubMed1982

Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change.

In a double-blind crossover design, the effect of cimetidine on oral diazepam pharmacokinetics and an evaluation of cognitive function change was studied in seven healthy volunteers. Subjects randomly received placebo or cimetidine 300 mg orally every 6 h for a total of five doses prior to diazepam 10 mg. A significant increase in diazepam elimination half-life from (mean +/- s.e. mean) 66.9 +/- 21.4 to 89.6 +/- 22.5 h (P = 0.006) and area under the plasma concentration-time curve from 5.06 +/- 1.47 to 8.93 +/- 1.88 micrograms ml-1 h (P = 0.028) was observed indicating a probable cimetidine induced inhibition of diazepam hepatic metabolism. Digit symbol substitution and visual analogue scales were used to measure the effect of an alteration of diazepam kinetics on cognitive function. An enhancement of pharmacological effect as reflected in digit symbol substitution scores and visual analogue scale measurements was not observed.

Administration, Oral↗
PubMed1982

Preparation and stability of indomethacin solutions.

Indomethacin is used in closure of the ductus arteriosus in newborn humans as well as in related research in near-term sheep and goats. Conflicting data in these studies have led to a reexamination of indomethacin stability. Solutions at various pH values, at two temperatures, and in polyethylene glycol (PEG-400), were assessed by high-pressure liquid chromatography for indomethacin and its products. Solutions below pH 7.4 were stable. Decomposition was rapid in alkaline solutions. Solutions at pH 7.4 showed no changes up to 24 h. Solutions of sodium indomethacin, and of indomethacin in PEG were stable. Solutions in aqueous Na2CO3 were variably stable depending on the mode of mixing. A solution prepared directly in 0.1 M Na2CO3 (pH 10.7) lost 75% of its content in 80 min; a similar solution diluted immediately with two volumes of pH 7.4 buffer (final pH 9.9) showed less decomposition. A solution in Na2CO3 adjusted to pH 7.4 with HCl was stable (at least 24 h). Solutions prepared by suspending indomethacin in 0.9% NaCl and adding Na2CO3 slowly were stable for 80 min; rapid mixing led to decomposition. Solutions in plasma were stable at -20 degrees C (2 months). Lack of indomethacin activity in some biological studies may have resulted from injection of inactive solutions.

Drug Stability↗
PubMed1981

Bratton-Marshall and liquid-chromatographic methods compared for determination of sulfamethazine acetylator status.

Synthesis of acetylsulfamethazine has made possible an evaluation of the Bratton-Marshall assay for this compound. Hydrolysis is an essential step in the assay, which depends on color development with the sulfamethazine formed in the hydrolysis. Sulfamethazine decomposes under the conditions needed for hydrolysis of acetylsulfamethazine, and this leads to depressed values for acetylsulfamethazine and to low figures for clinical "percent acetylation." Because of this, a simple "high-pressure" liquid-chromatographic procedure was developed for the assay; it requires no hydrolysis, is rapid in application, and can be applied to as little as 10 microL of capillary blood obtained by finger-to-puncture. We found that the cutoff point between "slow" and "fast" acetylators, when this method was used on samples from 75 subjects collected about 6 h after dosage, was 40% "acetylation" in plasma.

Adult↗
PubMed1979

Drug concentrations in neuropsychiatry. Methodological pitfalls: the influence of experimental design on results.

The valid study of relationships between pharmacokinetic measurements and clinical effects of psychotropic drugs depends on: (i) analytical methods for the drugs; (ii) the fluid assessed and pharmacokinetic derivations; (iii) clinical assessments and the nature of psychiatric illness; and (iv) statistical work. Standard problems with analytical methods include lack of specificity, unjustified claims for sensitivity, and failure to recognize metabolites as potential analytical contaminants and compounds for separate study. Problems with pharmacokinetic derivations include inappropriate calculations and incorrect assignment of terms such as 'half-life'. Clinical difficulties mostly relate to variations between patient groups, selection procedures and rating methods, and to timing of samples. Statistical controversies concern the calculation of metabolite ratios, pooling of data from drugs and their metabolites, and abuse of statistical techniques. These methodological problems are illustrated by reference to work with phenothiazines, tricyclic antidepressants, lithium, benzodiazepines and anticonvulsants.

Body Fluids↗
PubMed1979

Pharmacokinetics of closely related benzodiazepines.

1 It is commonplace for drugs to vary by only minor chemical differences. This is particularly so for those seven benzodiazepines discussed in this paper which are related both as precursors and as metabolites. However, minor chemical differences may cause major differences in physicochemical and pharmacodynamic properties. 2 Although the physicochemical differences are difficult to relate to effect, the influence of structure on absorption, distribution and elimination is of considerable importance in governing duration of effect, as shown by studies in monkeys and in man. This in turn dictates the suitability of a particular drug as a day or night sedative, as an anticonvulsant, or as an anxiolytic. 3 Structure affects the relative potency of the compounds as anticonvulsants, anxiolytics or sedatives so that judicious choice of a particular compound for a particular patient and condition will lead to improved therapy. It is fallacious to consider all benzodiazepines as similar.

Anti-Anxiety Agents↗
PubMed1979

Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man.

1 Fluphenazine (1,2-ethanol 14C) was administered to seven human subjects as the dihydrochloride and as the enanthate and decanoate esters. 2 The subjects had previously been treated with fluphenazine injections for at least 6 months. 3 Fluphenazine was separated from its radioactive metabolites by selective solvent extraction. Plasma concentrations were measured for up to 21 days after dosing. 4 The preparations showed differences in peak concentrations, times of the peaks and half-times of the elimination phase. The longest half-times occurred with the decanoate and the shortest with the dihydrochloride. 5 It is postulated that the differences in kinetics relate principally to the release of the compound from the site of injection. 6 There was no evidence for presence of the esters in plasma, urine or faeces.

Adult↗
PubMed1978

Trials of lithium, chlorpromazine and amitriptyline in schizoaffective patients.

Two drug trials in schizoaffective patients are reported. Nineteen "schizomanic" patients were treated for one month, on a double blind basis, with chlorpromazine or lithium and 41 "schizodepressive" patients with amitriptyline, chlorpromazine or both. In the schizodepressive patients there was a trend to a better response to chlorpromazine, but drug response generally was poor, only 20 per cent of patients recovering within the month. In the schizomanic patients lithium seemed as effective as chlorpromazine, which supports the view that these patients were suffering from a variant of mania.

Amitriptyline↗