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Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

At least 73 records · Page 4Linked to original sources
PubMed1990

Pharmacokinetics and pharmacodynamics of the ace inhibitor benazepril hydrochloride in the elderly.

The pharmacokinetics and pharmacodynamics of a single oral dose benazepril.HCl 10 mg have been studied in 15 healthy volunteers aged 65 to 80 y. The kinetics of unchanged benazepril and its active metabolite benazeprilat did not differ significantly in males and females, so the combined kinetic data from all 15 elderly subjects were compared with a historical control group of 19-32 year-old healthy men treated in the same way. The disposition of benazepril was not affected by age. The time to maximum plasma concentration, tmax (0.5 h) and elimination half-life (0.6 h) in the elderly were the same as in young subjects. The kinetics of benazeprilat was slightly changed in the elderly; although its tmax (1.5 h) was not affected, Cmax and the AUC were 20-40% greater. The elimination half-life of benazeprilat during the first 24 h after dosing in the elderly was increased by about 20% to 3.2 h. The renal plasma clearance of benazeprilat (18.1 ml.min-1) was about 20% smaller than in the young subjects. An average of 18.5% of the dose was recovered as benazeprilat in the 24 h urine from the elderly subjects, which was similar to the recovery in the young subjects. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 95%, respectively). Mean systolic and diastolic blood pressures in the elderly were reduced by a maximum of 37/16 mm Hg at 6 h, in association with a small rise in pulse rate. Treatment was generally well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Comparison of human, bovine, and newborn calf serum in the preparation of external quality assurance samples for therapeutic drugs.

The accuracy and precision of drug measurements made by different analytical techniques of a range of eight antiepileptic drugs, four tricyclic antidepressants, theophylline, and digoxin in three different matrices, human, bovine, and newborn calf serum, were compared using data reported to the Heathcontrol External Quality Assurance Scheme over 18 months. Neither of the animal serum samples was universally satisfactory compared with human serum. The newborn calf serum sample produced results that were closer to the spiked drug concentrations than those in bovine serum for most of the analytes covered by the survey. Both animal samples were unsuitable for digoxin, for which the use of scarce human material is recommended.

Animals↗
PubMed1990

Effect of gamma aminobutyric acid on the carbon dioxide rebreathing response of normal subjects: a study using vigabatrin.

Animal studies suggest that gamma aminobutyric acid (GABA) may be an important neurotransmitter in the control of respiration. Vigabatrin, a new drug for the treatment of epilepsy, is thought to exert its effect by increasing GABA concentrations in the brain. To assess the effect of increased GABA concentrations in the brain on human respiration we measured the ventilatory response to carbon dioxide in seven normal subjects after they had taken vigabatrin or placebo for three days in a double blind crossover study. There was no change in either the slope or the intercept of the curve of the ventilatory response to carbon dioxide after vigabatrin by comparison with placebo. This study suggests that GABA does not have an important role in the control of respiration in normal individuals.

4-Aminobutyrate Transaminase↗
PubMed1990

A survey of drugs of abuse testing by clinical laboratories in the United Kingdom. Steering Committee for the UK-External Quality Assessment Scheme for Therapeutic Drug Assays.

An external quality assessment survey of testing facilities in UK clinical laboratories for the detection of drugs of abuse was made with nine freeze-dried samples of urine containing representative drugs with their metabolites from the following seven classes; amphetamines and stimulants, barbiturates, cannabinoids, cocaine, minor tranquillisers, opiates and non-opiate narcotics. Reports were received from 120 laboratories. Thirty six per cent of laboratories reported on all seven drug classes and 71% on the five classes excluding cannabinoids and cocaine. A single drug screening technique was used by 32% of laboratories whilst 46% were able to perform tests by both immunological and chromatographic techniques. There was a mean level of false positive reporting of 4.3% and an observed level of false negative reports of 8.4%, the latter underestimating the true frequency. The minor tranquillisers, cocaine and benzoyl ecgonine were the most frequently missed analytes. Several false reports had important potential implications for patient care.

Central Nervous System Agents↗
PubMed1989

A study of inter-reviewer reliability of attacks recorded on ambulatory EEG.

Eleven ambulatory EEG (A/EEG) cassette tapes were sent to 5 reviewers from different EEG laboratories in the U.K. Each tape included one attack recorded from a different patient. Attacks were chosen to include various possible EEG changes that can occur during attacks on A/EEG. Reviewers were asked to give details of EEG changes seen during attacks and to state whether they thought attacks were epileptic. Total agreement about the presence of abnormality was found on 2 tapes. Four out of 5 reviewers agreed on 4 tapes and on the remaining 5 tapes only 2 or 3 reviewers were in agreement. It was concluded that the amount of agreement amongst reviewers was poor but reasonable in view of the degree of difficulty of the tapes which were not a random sample. Compared to the final clinical opinion of referring consultants, these findings would have resulted in 16% false negatives, 7% false positives and 13% of cases in which no decision was made.

Ambulatory Care↗
PubMed1989

Evaluation of assay techniques for the measurement of antiepileptic drugs in serum: a study based on external quality assurance measurements.

The accuracy and precision of eight techniques used to measure a range of eight antiepileptic drugs in human serum were compared using data from 80 samples from the Heathcontrol External Quality Assurance scheme. The fluorescence polarization immunoassay was significantly more precise than other techniques for several analytes, producing the lowest number of measurements rejected as outliers and measurements with the lowest coefficient of variation. Other techniques had a significantly lower precision. Nephelometry (Neph) produced most outliers for phenytoin and carbamazepine and had the highest variability for phenytoin. Gas-liquid chromatography (GLC) with derivatization was most variable for phenobarbitone and primidone. Measurements by GLC with or without derivatization contained greater than 10% of outliers and were least precise for carbamazepine. Differences between the majority of techniques were in many cases, however, not significant. The accuracy of techniques was assessed from differences between sample means and spiked drug concentrations. Neph was notable in producing overestimates at lower concentrations. Immunoassay methods had a 16-21% cross-reactivity with carbamazepine 10,11-epoxide when measuring carbamazepine. All techniques reported underestimates for valproic acid that were thought to result from the hygroscopic nature of the salt used for spiking.

Anticonvulsants↗
PubMed1989

External quality assurance of tricyclic antidepressant measurements in serum: eight years of progress?

Comparison of the precision and accuracy of measurements made between December 1979 and January 1988 of tricyclic antidepressant drug concentrations in freeze-dried external quality-assurance samples of human serum showed only occasional significant differences between the different chromatographic techniques used for drug assay. Larger differences between data collected in different years correlated with changes in the source of the sample matrix and the personnel responsible for sample preparation. Measurements of amitriptyline and imipramine were more precise than those of nortriptyline and desipramine; the mean coefficients of variation of measurements were 20.2, 19.6, 26.6 and 25.3%, respectively. The data indicate the need for further interlaboratory studies directed at reducing the high level of variability in tricyclic measurements.

Amitriptyline↗
PubMed1989

Interaction between vigabatrin and phenytoin.

1. The study was designed to determine the mechanism by which vigabatrin causes a fall in plasma phenytoin concentrations when added to the drug therapy of eight epileptic patients. 2. Total plasma phenytoin concentration was measured before and at intervals during 5 weeks' treatment with vigabatrin. 3. Plasma protein binding of phenytoin, the urinary ratio of phenytoin to 5-(p-hydroxyphenyl)-5-phenylhydantoin, and antipyrine clearance were measured before and at the end of treatment period. 4. Mean plasma phenytoin concentration fell significantly by 23% during the fifth week. 5. No change was found in any of the other measures. 6. Although an interaction between phenytoin and vigabatrin has been confirmed, the mechanism has not been elucidated.

Adolescent↗
PubMed1989

The effect of vigabatrin on brain and platelet GABA-transaminase activities.

1. The inhibition profiles of GABA-transaminase (GABA-T) in rat brain and platelet have been compared following a single intraperitoneal dose of vigabatrin. The inhibition profiles exhibit similarities. The inhibition produced by the drug is dose-dependent and, in the dose range used in man, the dose-response curves are comparable. The pharmaco-dynamic effects of the drug (inhibition of central and peripheral GABA-T) remain after the drug has been eliminated from plasma. It is suggested that the measurement of rat platelet GABA-T may be used as a non-invasive assessment of the efficacy of GABA-T inhibitors in the rat CNS. 2. Human blood platelet GABA-T was significantly inhibited by the administration of a single oral dose of vigabatrin. Chronic administration also produces a significant inhibition of platelet GABA-T. As with rats, the pharmacodynamic effects on the platelet enzyme remained after the drug had been eliminated from plasma. If the situation in man is assumed to parallel that found in the rat then measurement of platelet GABA-T inhibition could prove to be a useful indicator of central inhibition.

4-Aminobutyrate Transaminase↗
PubMed1989

Disposition of anticonvulsants in childhood.

There have been great advances in our understanding of the childhood epilepsies within recent years and at the same time there has been increasing awareness of the pharmacokinetic properties of the anticonvulsant drugs. It has been increasingly recognised that pharmacokinetic parameters of anticonvulsants are not constant, but are subject to influences by a number of physiological variables over which age is a major determinant. As changes in pharmacokinetic parameters will alter dosage requirements, dosage regimens cannot be transferred from one age group to another without the risk of underdosing or overdosing. Drug monitoring techniques are being increasingly used as a guide to correct dosing but knowledge of the limitations of monitoring is as important as knowledge of potential benefits for monitoring to be used correctly. An overview of the important pharmacokinetic properties of anticonvulsant drugs is provided, with emphasis on findings in children where such data are available.

Adolescent↗
PubMed1989

Comparison of nonisotopic and radioimmunoassay techniques for digoxin: a study based on external quality assurance measurements.

A comparison of the precision and accuracy of three nonisotopic and of radioimmunoassay (RIA) techniques for digoxin was made using data from 141 samples of spiked human serum assayed between 1984 and 1987 by members of the Heathcontrol external quality assurance scheme. There were significant differences between techniques in the number of observations rejected as outliers greater than 3 SD from the sample mean, the percentages of rejected measurements being Abbott TDX 1.4, RIA 3.3, Ames TDA 4.2, and Syva EMIT 6.3. Ames TDA and Syva EMIT were shown to have a significantly lower precision than the other techniques in measurements of digoxin concentrations less than 1 nmol/L. A significant 4% negative bias was observed for Ames TDA measurements of digoxin concentrations between 1 and 2.6 nmol/L. A concentration-related bias was demonstrated for Abbott TDX measurements that varied from 14% overestimates at concentrations less than 1 nmol/L to 6.7% underestimates of digoxin at concentrations greater than 2.6 nmol/L.

Digoxin↗
PubMed1988

Evaluation of chromatographic and kit immunoassay techniques for the measurement of theophylline in serum: a study based on external quality assurance measurements.

The accuracy and precision of assay techniques used to measure theophylline concentrations in human serum were compared using data from 96 samples from the Heathcontrol external quality assurance scheme. Abbott TDX had the highest precision, with a mean coefficient of variation (CV) of measurements of 6.4%, and Ames Fluorostat was most accurate, with a mean bias of +0.1%. Differences between the better techniques, however, were not significant. The Beckman ICS assay gave the lowest precision (CV 9.3%) and, in addition, produced the highest proportion (7.5%) of rejected observations greater than 3 standard deviations from the sample mean. The least accurate method was radioimmunoassay, with a -9.9% bias. Measurements from two samples spiked with paraxanthine demonstrated that 76% of laboratories using high-pressure liquid chromatography (HPLC) were unable to distinguish between paraxanthine and theophylline. The +4% bias observed at low concentrations and the high variability (CV 8.3%) of measurements made by HPLC were thus attributed to interference by paraxanthine present in the sample matrix. Discriminant analysis of a range of HPLC column and mobile phase parameters indicated that separation of theophylline and paraxanthine was achieved by the use of lower flow rates with mobile phases of solvent mixtures with lower proton donator selectivity.

Chromatography, High Pressure Liquid↗
PubMed1988

Inhibition of the enzyme, GABA-aminotransferase in human platelets by vigabatrin, a potential antiepileptic drug.

1. The effect of the new antiepileptic drug, vigabatrin (gamma-vinyl GABA), on the platelet enzyme, GABA-aminotransferase (GABA-T) was investigated in volunteers and patients. Platelets GABA-T activity was assayed using a radioenzymic method. 2. Three single oral doses of vigabatrin (1 g, 2 g and 4 g) were given to six healthy male volunteers in an open randomised cross over study and compared with a baseline period preceding the three treatments. 3. Significant inhibition of the platelet GABA-T was produced by treatment with all three doses and a dose-response relationship was demonstrated. The minimum enzyme activities after 1 g, 2 g and 4 g doses were 43%, 30% and 21% respectively compared with the control values. 4. A significant depression of enzyme activity occurred at 30 min after drug administration and the values remained below control values for 72 h post-dose, outlasting the presence of the drug itself in the plasma. 5. Eight patients with chronic refractory epilepsy were treated with vigabatrin for 6 weeks. After taking the 2 g daily dose for 1 week there was a marked reduction in platelet enzyme activity in all subjects but the enzyme inhibition produced by the 3 g dose was not significantly different from that produced by the 2 g dose, even after 4 weeks treatment with the larger dose. The mean enzyme activity was approximately 30% throughout the active treatment period. One week after stopping vigabatrin, the enzyme levels were not significantly different from the baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobutyrate Transaminase↗
PubMed1988

Haematological values of epileptic patients entering drug trials.

Retrospective comparison of peripheral haematological values in normal volunteers and patients on anti-epileptic drugs over a one year period demonstrated a significant reduction in total white blood cells, neutrophil, eosinophil, lymphocyte and monocyte counts in patients. The red blood cell count, mean cell volume and mean cell haemoglobin were significantly reduced in the patients. These findings need to be taken into account when new anti-epileptic drugs are assessed by adding on to existing therapy.

Adolescent↗
PubMed1987

Micro-vacuolation in rat brains after long term administration of GABA-transaminase inhibitors. Comparison of effects of ethanolamine-O-sulphate and vigabatrin.

Two "suicide" inhibitors of GABA-aminotransferase which are known to raise the concentration of GABA in vivo and to have anti-convulsant properties, have been compared for the extent to which they produce micro-vacuoles in the brains of rats. The compounds gamma-vinyl-GABA (Vigabatrin) and ethanolamine-O-sulphate were administered orally for six months to rats at doses that produced the same increase in brain GABA levels. Micro-vacuolation was found to be present in the brains of animals treated with either compound but to be more severe in those treated with Vigabatrin. A quantitative assessment using computerised image analysis revealed that both the number of vacuoles, and the area occupied by them, was twice as high in the Vigabatrin treated animals as in those treated with ethanolamine-O-sulphate. This quantitative difference could be seen to be due to the fact that in the Vigabatrin treated animals the vacuoles extended into the white matter tracts between the cerebellar folia whereas in those animals treated with ethanolamine-O-sulphate it was confined to the roof nucleus.

4-Aminobutyrate Transaminase↗