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Biomedical subjects

G J Wright

Publications and source records attributed to G J Wright.

At least 37 records · Page 2Linked to original sources
PubMed1984

Simultaneous determination of fluzinamide and three of its active metabolites in plasma by high-performance liquid chromatography.

A sensitive and selective high-performance liquid chromatographic method has been developed for a new anticonvulsant, fluzinamide, and three of its active metabolites. This method requires only 0.5 ml of plasma, and it involves a single extraction with a mixture of hexane--dichloromethane--butanol (55:40:5). The plasma extract is chromatographed on a 10-micron, C18 reversed-phase column and quantitated by ultraviolet absorbance at 220 nm. The concentration--response curves for all four compounds are linear from 0.05 micrograms/ml to at least 10 micrograms/ml. The extraction efficiency of this method is greater than 90%. The accuracy and precision of the method were tested by analyzing spiked unknown samples that had been randomly distributed across the concentration range. The mean concentrations found were within +/- 9% of the various amounts added with a standard deviation of +/- 3.5%. This method has been successfully applied to the analysis of samples obtained from fluzinamide-dosed dogs, healthy unmedicated volunteers, and patients who were at steady state with phenytoin, carbamazepine, and fluzinamide.

Anticonvulsants↗
PubMed1982

Metabolic disposition of terfenadine in laboratory animals.

Alpha-[4-(1,1-Dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1- piperidinebutanol (terfenadine, RMI 9918, Triludan, Teldane, resp.), a clinically effective antihistamine, with little or no central nervous system effects, was investigated in order to understand its metabolic disposition. These 14C-terfenadine studies were performed in laboratory animals, principally the rat, and also in beagle dog and monkey (Macaca mulatta). In all three species the fecal pathway of excretion was predominant with nearly all the elimination occurring within 24 h of administration. The data suggest that biliary excretion plays a prominent role. Tissue distribution studies indicated that the liver and lung, relative to other tissues, exhibited the highest concentrations of 14C-terfenadine equivalents. However, brain had low amounts of 14C-terfenadine which was in general agreement with the whole-body autoradiographic studies which did not show radioactivity in brain or spinal cord. The evidence suggests that terfenadine was metabolized rapidly with no terfenadine in urine or bile and small amounts in feces. Tissue concentrations of terfenadine were in the low nanogram range and peaked at 0.5-1.0 h with lung exhibiting the greatest and the brain sub-quantifiable amounts. The ratios of 14C-terfenadine eq/terfenadine were high and greatest in the liver and kidney. These studies demonstrated that terfenadine was readily absorbed and eliminated, virtually had undergone complete biotransformation and exhibited very low tissue concentrations per se.

Animals↗
PubMed1980

A multiple-scan high resolution mass spectrometer data system for the analysis of mixtures: the analysis of morphine in liver.

A high resolution mass spectrometer operating with a laboratory data system in multiple scan mode allows the generation of high resolution evaporation profiles for any m/z value. The system allows fast qualitative and quantitative analysis of components of complex mixtures. System performance is evaluated by analysis of morphine in liver samples; a precision of 15% at the 0.1 microgram g-1 level is obtainable on post-mortem samples.

Cadaver↗
PubMed1980

Radioimmunoassay for terfenadine in human plasma.

A radioimmunoassay procedure was developed for the antihistamine terfenadine (alpha[4-(1,2-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol). The keto analog of terfenadine was converted to its O-carboxymethyloxime derivative, which was conjugated to bovine thyroglobulin by a mixed anhydride technique. Rabbits were immunized with the resulting conjugate, and antiserums capable of binding radiolabeled terfenadine were obtained. Tritium-labeled terfenadine was prepared by a combination of exchange and reduction with platinum oxide in the presence of tritium gas, and the procedure yielded a specific activity of 48 Ci/mmole. Plasma containing terfenadine was diluted with sodium carbonate solution and extracted with hexane, and the hexane extracts were evaporated and analyzed. The between-assay coefficient of variation on control samples ranged from 8% at 10 ng/ml to 14% at 1 ng/ml. The lower practical sensitivity limit was at least as low as 0.25 ng/ml (25 pg measured). Two metabolites of terfenadine cross-reacted 16-30% with the antiserum used. However, extraction eliminated essentially all of these compounds. Analysis of plasma samples from human subjects given terfenadine showed marked intersubject variability and low plasma levels.

Benzhydryl Compounds↗
PubMed1980

Effects of oral perhexiline on canine myocardial flow distribution.

Perhexiline maleate at a dose of 400 mg three times daily for 2 days administered to normal dogs altered the relative regional transmural resistance so that during reduced coronary flow the endocardium:epicardium (endo:epi) ratio is increased. In the presence of acute myocardial infarction heart rate was significantly lower and the endo:epi ratio of perfused areas was increased when coronary flow was normal. A linear relationship was observed between the endo:epi ratio and the concentration of perhexiline in plasma, and its monohydroxyl metabolite in plasma. The results suggest that the mechanism of action of the drug is due to redistribution of a limited coronary flow.

Animals↗
PubMed1977

Mass spectra of some specifically deuterated tryptamines.

The mass spectra of the four tryptamine derivatives, N-acetyl-5-methoxytryptamine (melatonin), N-acetyl-5-hydroxytryptamine (N-acetyl-serotonin), N,N-dimethyl-5-hydroxtryptamine (bufotenine) and N,N-dimethyl-5-methoxytryptamine (O-methylbufotenine), with specifically labeled [D4] aminoethyl sidechains have been measured. Comparison of these spectra with those of the unlabeled compounds enable the major fragmentations of the compounds to be defined.

Bufotenin↗
PubMed1975

The objective and timing of drug disposition studies, appendix II. Plasma concentrations of oxyphenbutazone in dogs given oxyphenbutazone or the calcium or sodium salts of its phosphate ester.

Plasma levels of oxyphenbutazone were measured in beagle dogs following oral administration of oxyphenbutazone and salts of oxyphenbutazone phosphate. Dosage with sodium and calcium salts of oxyphenbutazone phosphate produced higher oxyphenbutazone plasma levels than dosage with oxyphenbutazone itself. Oxyphenbutazone phosphate was not detected in plasma following oral dosing with salts of oxyphenbutazone phosphate but was found in plasma following intramuscular administration of oxyphenbutazone phosphate sodium salt. A metabolite, oxyphenbutazone glucuronide, was found in plasma of dogs following administration of either oxyphenbutazone or salts of oxyphenbutazone phosphate.

Administration, Oral↗
PubMed1975

The objective and timing of drug disposition studies, appendix III. Diethylpropion and its metabolites in the blood plasma of the human after subcutaneous and oral administration.

Diethylpropion hydrochloride is an effective anorexiant at the recommended dose of 25 mg three times a day. Previous work in volunteers to evaluate the effects of much larger doses showed that 400 mg given orally was equipotent with 600 mg subcutaneously in terms of subjective and physiologic effects, i.e., the drug was more potent orally than subcutaneously. In one volunteer, blood level studies after a 600-mg subcutaneous dose showed concentrations of unchanged diethylpropion in the plasma about three times as high as those found after the equipotent 400 mg oral dose. In nine other volunteers, the plasma concentrations of unchanged diethylpropion found after a 75-mg oral dose was less than 1/100 of that observed after a 400-mg oral dose. These observations suggest a rapid but limited metabolic capacity for conversion of diethylpropion to its metabolites. The data indicate that the metabolites, rather than the parent drug, are responsible for the pharmacologic responses seen with doses much larger than those necessary for inducting anorexia.

Administration, Oral↗
PubMedDate not supplied

Bioavailability of terfenadine in man.

Fourteen normal male subjects were given either 60mg or 180mg of terfenadine suspension in a randomized two-way crossover study. Peak plasma concentrations of 1.544 +/- 0.726 (mean +/- S.D.) ng ml-1 were obtained in 0.786 h following the 60 mg dose and displayed an AUC or 11.864 +/- 3.369 ng h ml-1. Whereas peak plasma concentrations of 4.519 +/- 2.002 ng ml-1 in 1.071 +/- 0.514 h were obtained following the 180 mg dose. The AUC following the 180 mg dose was 44.341 +/- 22.041 ng h ml-1. When 60 mg of 14C terfenadine was given to six additional subjects, the peak plasma concentrations of 351 +/- 43 ng equivalents per ml were obtained in 1.67 +/- 0.41 h and the AUC was 2297.71 +/- 310.85 ng-equivalents h ml-1. This indicates that approximately 99.5 per cent of the terfenadine related material that is absorbed undergoes biotransformation. Urinary excretion of 14C accounted for 39.89 +/- 5.29 per cent of the dose while 60.58 +/- 2.44 per cent of the dose was recovered in the feces in twelve days. Thin-layer chromatographic (TLC) examination of fecal extracts showed only a trace of material chromatographing with terfenadine. This may indicate that the 14C present in the feces is not due to lack of absorption.

Benzhydryl Compounds↗
PubMedDate not supplied

Comparative quinidine plasma profiles at steady state of two controlled-release products and quinidine sulfate in solution.

A study was conducted to compare, at steady state, the plasma quinidine level profiles of two commercial controlled-release products (quinidine sulfate controlled release and quinidine gluconate controlled release) with quinidine sulfate given in solution. Twenty-four healthy volunteers entered the study and 23 completed it. Quinidine formulations were given at 600 mg day-1 for 4 days in each of three periods in a randomized crossover study. In addition to frequent blood sampling on the fourth day of each period, samples were taken during the approach to steady state to confirm by minimum plasma concentrations (Cmin) that steady state had been attained. Quinidine concentrations were measured by using a high-performance liquid chromatographic assay specific for quinidine. The bioavailability of the two controlled-release products relative to quinidine sulfate in solution was adequate when dose correction to account for differences in quinidine base content was done. Without dose correction, the area under the plasma concentration-time curve (AUC) for the quinidine gluconate form was 85 per cent that of the solution: an amount equivalent to the relative actual amount of quinidine base in the quinidine gluconate dosage form. The maximum plasma concentration (Cmax), Cmin, peak-to-trough differences, and AUC from the quinidine sulfate extended-release form given 300 mg q12h were similar to the solution given 150 mg q6h. With dose correction, the quinidine gluconate controlled-release form given q12h had equivalent AUC but larger peak-to-trough differences than either the quinidine sulfate extended-release product given q12h or quinidine sulfate in solution given q6h.

Adult↗