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Biomedical subjects

M Mitchard

Publications and source records attributed to M Mitchard.

At least 19 recordsLinked to original sources

Sulphur compounds used in medicine.

Native sulphur has had limited success as a medicinal agent. There is, however, hardly a class of drugs which does not contain compounds having sulphur in their structure. Sulphur-containing dyes have given rise to many clinically useful substances, others, such as the -lactam antibiotics, have been developed from naturally occurring molecules and yet others have been designed on the basis of a detailed understanding of physiological mechanisms. Sulphur occurs in drug molecules in all its oxidative states and in all its forms of organic combination. Organo-sulphur compounds, unquestionably form a major therapeutic resource and their potential remains to be further exploited.

Animals

Bioavailability of chlorpropamide.

1. The serum profiles of chlorpropamide obtained following single doses of two tablet preparations and from a suspension formulation have been compared in healthy volunteers. The amounts of chlorpropamide absorbed from the three formulations were similar but the drug was absorbed more rapidly from the suspension than from either tablet formulation. There was a small but therapeutically insignificant difference in the rate of absorption of the drug from the two tablets. 2. Changes in blood glucose concentrations were found to be related to the drug serum profile characteristics of the formulations.

Adolescent

Quantitative determination of tiflorex in human fluids using electron-capture detection.

A procedure is described for the determination of tiflorex and its metabolite nortiflorex in biological specimens. The compounds are converted into their trichoroacetyl derivatives, which are separated on a glass column packed with 3% OV-17 on Gas-Chrom Q, and measured with an electron-capture detector. The mechanism was investigated by gas chromatography-mass spectrometry. The method is rapid, sensitive for concentrations of 1 ng/ml and has been used to measure tiflorex and its metabolite in rat plasma after intravenous administration and in human volunteers after administration by the oral route.

Animals

Simple sensitive and specific gas chromatographic method for the quantification of diltiazem human body fluids.

A gas cromatographic method for the determination of the benzothiazepine diltiazem together with its major metabolite desacetydilitiazem, is described. Silylation of the desacetyl derivative separates the metabolite from the parent drug on a 1% OV-17 column and cyclopam is used as an internal reference standard. The compounds are analysed by means of a nitrogen detector which allows the determination of 10 ng/ml of both compounds in plasma. The method has been used to determine both diltiazem and its desacetyl derivative in plasma obtained from healthy volunteers after oral doses of 60-210 mg of diltiazem.

Benzazepines

Mecillinam serum levels following intravenous injection: a comparison with pivmecillinam.

Serum mecillinam concentrations have been obtained in 6 volunteers after intravenous injection of 200 mg mecillinam and two 200 mg tablets containing pivmecillinam hydrochloride. Initial concentrations were between 6 and 9 mg/1 and peak concentrations of about 2-0 mg/1 occurred at 1 to 1-5 h after the tablets. Analysis of the intravenous data shows the concentration/time curve to be biphasic and similar to that previously reported for penicillin G. The biexponential curves describing the data have been calculated using nonlin. Comparison of the areas under the serum mecillinam concentration/time curves suggests a bioavailability of 65 to 70% for the tablets. However, the two preparations contain therapeutically equivalent amounts of antibiotic, as two 200 mg tablets of pivmecillinam contain 30% more mecillinam than the 200 mg injection.

Adult

The disposition of sodium fusidate in man.

1 In a pharmacokinetic study in six volunteers serum fusidic acid concentrations were obtained after rapid intravenous administration of 100 mg. 2 Analysis of the data suggests that the serum concentration/time curve is biphasic and that the curve can be described by the following equation: cp=5.9e(-1.82t)+4.3e(-0.13t). 3 The disposition characteristics of sodium fusidate have been calculated from this relationship and a plasma half life for sodium fusidate of between 5 and 6 h obtained. 4 Subsequently plasma fusidic acid levels have been measured in the same volunteers on three occasions after sodium fusidate (500 mg) given either as a slow intravenous infusion, or orally as a capsule or as a suspension. 5 Serum levels and AUC after a capsule were about 75% of those obtained after the infusion (30 and 70 mg/1 at peak respectively) whereas levels and AUC after the suspension were only about 50%.

Adult

The influence of alcohol on the persistent effects on human performance of the hypnotics Mandrax and Nitrazepam.

Psychotropic drugs are prescribed to modify human behavior but they have persistent central sedative activity which may become a troublesome side-effect. Alcohol is known to interact with psychotropes, often to potentiate their central effects. We have previously shown that residues of some hypnotic drugs persist in the body for up to a week after a single therapeutic dose and have demonstrated that alcohol decreases the elimination rate of methaqualone even when taken 2 or 3 days after the drug. We have therefore looked at the influence of alcohol on the residual effects of Mandrax and nitrazepam on three measurements of human performance. The study was a double-blind, 3-way, cross-over study in which the following treatments were used: drug + alcohol, drug + alcohol placebo, and drug placebo + alcohol. In each case the alcohol or alcohol placebo was given 1, 2, and 3 days after the drug or placebo. The subject's kinetic visual acuity was measured 40 minutes after the alcohol had been taken. This was followed by a Stroop test. Changes in mental state and arousal were measured by an 18-item visual analogue scale. An interaction between alcohol and Mandrax was apparent in the results obtained from the Stroop and visual analogue scale on the third day. However, no interaction with nitrazepam could be clearly demonstrated by any of the tests on any occasion. The application of these results to the "real life" situation is discussed.

Adult

A comparison of slow release with conventional oxprenolol: plasma concentrations and clinical effects.

1 Plasma concentrations of oxprenolol have been compared in six healthy volunteers after 80 and 160 mg doses of a new slow release (SR) oxprenolol preparation, after an 80 ng dose of conventional oxprenolol (CO), and after the second of two 80 mg doses of conventional oxprenolol given 12 h apart. Basal pulse rates and blood pressures, and pulse rates before and after a standard exercise test have been compared after the four active treatments and after a placebo. 2 Peak plasma concentrations of oxprenolol attained after 160 mg of the slow release preparation were similar to the peak concentrations after the single 80 mg dose of conventional oxprenolol. Higher concentrations, however, persisted for much longer after the slow release preparations than after the conventional preparations. 3 Neither oxprenolol formulation had any effect on resting pulse rate or blood pressure in normotensive volunteers. 4 Comparison with placebo showed that the single dose of the conventional oxprenolol produced a significant reduction in exercise induced tachycardia for 8 h whereas the high dose of the slow release preparation produced a similar reduction which lasted for at least 14 hours.

Administration, Oral

General pharmacokinetic equations for linear mammillary models with drug absorption into peripheral compartments.

General equations are derived for the disposition functions of any compartment in a linear mammillary model, when the system input occurs into a peripheral compartment. Laplace transforms and matrix algebra are used to derive these equations. Equations describing the time-course of a drug in any compartment are readily obtainable using disposition and input functions.

Intestinal Absorption