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Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

At least 19 recordsLinked to original sources
PubMed1979

Interpretation of drug levels: relevance of plasma protein binding.

Many centrally acting drugs bind extensively to plasma proteins, particularly albumin. It is generally the free concentration rather than the total concentration which determines the intensity of pharmacological action and the distribution and rate of elimination of a drug. Measurement of the total plasma concentration may therefore give a false idea of the amount of active drug available. Furthermore, variation in the degree of binding from one subject to another, and displacement of drug molecules by a second drug, may complicate the interpretation of serum levels when both bound and free drug are measured together. The strict use of therapeutic ranges of serum levels may therefore be harmful when a larger than normal proportion of the drug is free. In theory, monitoring the free concentration would have advantages, but on a routine basis this is not practical at present for technical reasons. Cerebrospinal fluid is an ultrafiltrate of plasma but lumbar puncture for routine monitoring purposes cannot be justified. Monitoring salivary concentrations is a practical alternative but for some drugs variation in the degree of ionization of the compound may make salivary levels unreliable.

Blood Proteins↗
PubMed1979

Quality control of drug assays.

Most routine drug assay work is done by clinical chemists who, in general, are well aware of the importance of regular quality control checks. Few, however, have had extensive experience in analytical techniques for drugs, such as gas chromatography, and often underrate the difficulty in obtaining reliable results. Although antiepileptic drugs are among the easiest to measure, a North American study organized by Dr Charles Pippenger and a European study performed by the author demonstrated clearly the poor quality of results coming from many laboratories. From these studies have grown two external quality control schemes which together involve over 800 laboratories on a world-wide basis. Reports have indicated that the reliability of theophylline, tricyclic antidepressant and phenothiazine assays is also poor, and it might be expected that the problems will increase as attempts are made to measure drugs present in lower concentrations. Careful attention to quality control will be essential if physicians are to be provided with reliable results.

Anticonvulsants↗
PubMed1979

Results of a quality control scheme for the assay of theophylline in serum.

Twenty-eight laboratories in the United Kingdom, Europe, and Australia participated in pilot study to assess interlaboratory variability in determining serum theophylline levels. Each laboratory received two samples of pooled serum containing theophylline each month and was asked to report their results and method to us. Data obtained over a period of 12 months were collated, enabling certain conclusions to be drawn. Five methods of analysis were used: high pressure liquid chromatography (HPLC), gas--liquid chromatography, EMIT, thin-layer chromatography, and ultraviolet spectroscopy (UV). All of these methods, with the exception of UV, were found to be satisfactory, with HPLC marginally superior. Several laboratories improved their assay techniques over the period of operation of the scheme, and all found the scheme helpful in assessing the performance of their methods.

Chromatography, Gas↗
PubMed1979

Predicting phenytoin dose - a revised nomogram.

The nomogram devised by Richens and Dunlop for predicting phenytoin dose has been tested in 127 residential epileptic patients, and the data obtained were used to prepare a revised version of the nomogram. In a further 78 patients, this new version was found to be superior to the original. The mean Km value was found to be 23.8 mumoles/liter. Km was independent of age and body surface area, but Dmax correlated positively with the latter two variables.

Adolescent↗
PubMed1979

Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.

1 The serum concentration profile of paracetamol has been determined after administration of single 1000 mg intravenous and oral doses in six normal subjects and six epileptic patients on chronic antiepileptic drug therapy. The urinary excretion of free and conjugated paracetamol has also been determined. 2 Following intravenous administration, serum paracetamol concentration declined with first-order kinetics. Both elimination rate and total body clearance were higher in the epileptic patients, although in neither case was the difference statistically significant. 3 The oral bioavailability (mean +/- s.e. mean) was significantly lower in the epileptic patients than in the normal subjects (0.77 +/- 0.03 and 0.89 +/- 0.02 respectively, P less than 0.01), whereas the urinary excretion total (free+conjugated) paracetamol was almost identical in the two groups. 4 It is suggested that the lower bioavailability of paracetamol in the epileptic patients results from enhancement of first-pass metabolism, secondary to enzyme induction.

Acetaminophen↗
PubMed1979

Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients.

1. The pharmacokinetics of lignocaine following single oral and intravenous doses have been investigated in six normal volunteers and in six patients receiving chronic antiepileptic drug therapy. 2. After intravenous administration, serum lignocaine levels declined biexponentially in all subjects. The serum clearance (mean +/- s.d.) was slightly higher in the patients (0.85 +/- 0.09 v 0.77 +/- 0.07 l/min) but the difference was not statistically significant. 3. Lignocaine bioavailability after oral administration was more than two-fold in the patients than in the normal subjects (0.15 +/- 0.06 v 0.37 +/- 0.09, P < 0.001). 4. It is suggested that the reduced bioavailability of lignocaine in the patients is a consequence of stimulation of hepatic first-pass metabolism by antiepileptic drugs.

Administration, Oral↗
PubMed1979

Theophylline: biochemical pharmacology and pharmacokinetics.

Theophylline and its derivatives, such as aminophylline, have an established role as bronchodilators, although their mode of action in man is not clear. There is circumstantial evidence that therapeutic doses of theophylline may have a phosphodiesterase inhibiting effect, thus potentiating the effects of cyclic AMP. However, it remains to be established whether this is the primary mode of action of theophylline at the biochemical level. The pathways of theophylline metabolism have been clarified, although most of the enzymes involved have not been characterized. Hepatic microsomal enzyme induction by polycyclic hydrocarbons will increase the rate of theophylline elimination. There are a number of factors which influence theophylline clearance in adults, which is known to be highly variable. These factors include obesity, smoking habit, diet and the presence of such diseases as hepatic cirrhosis, acute pulmonary oedema, cor pulmonale and viral respiratory infection. There is a good correlation between plasma theophylline level and bronchodilator effect. This can be demonstrated at plasma levels as low as 5 microgram/ml, although optimal levels are usually greater than 10 microgram/ml. Unacceptable toxicity usually occurs in association with plasma levels greater than 20 microgram/ml. The maintenance of adequate plasma theophylline levels by the use of a sustained-release aminophylline tablet is discussed.

Aminophylline↗
PubMed1978

Is phenytoin metabolism dose-dependent by enzyme saturation or by feedback inhibition?

The suggestion from animal experiments that phenytoin metabolism may be dose-dependent in man due to feedback inhibition by the major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, was examined in 3 normal subjects by measuring phenytoin clearance during an intravenous infusion of the metabolite and during a control infusion of solvent. Clearance was measured using both carbon-labeled and unlabeled phenytoin. The infusion of metabolite did not produce any consistent change of phenytoin clearance, suggesting that feedback inhibition does not occur in man.

Adult↗