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Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

At least 217 records · Page 12Linked to original sources
PubMed1977

Evaluation of a new immunoassay for determination of phenytoin and phenobarbital: results of a European collaborative control study.

The performance of a new enzyme multiplied immunoassay technique (EMIT) was compared with other current methods, namely gas-liquid chromatography and thin-layer chromatography, for the determination of phenytoin and phenobarbital in serum. Forty-three serum samples were sent as unknowns to the participating laboratories for determination. The precision of repeated determinations was very similar for EMIT and chromatography. There was good agreement among gas chromatography, thin-layer chromatography, and EMIT results. Interlaboratory variability was lower for EMIT determinations of both antiepileptic drugs. The rapid analysis of small samples, made possible by the EMIT system, could have beneficial effects on the treatment of epilepsies.

Chromatography, Gas↗
PubMed1977

Interactions with antiepileptic drugs.

Most of the currently available antiepileptic drugs have a low therapeutic ratio and therefore a drug interaction causing elevation of the serum level of one of these compounds can readily lead to drug intoxication. Phenytoin, in particular, is vulnerable because its metabolism is dose-related and at therapeutic serum levels the enzyme system involved in its degradation is easily inhibited by concurrent drug administration. As multiple drug therapy has traditionally been practised in the management of epilepsy, clinically important interactions are common. Furthermore, most of the drugs used in the treatment of major epilepsies are potent inducers of hepatic microsomal enzymes and can therefore stimulate the metabolism of concurrently-administered drugs to such an extent that they may be rendered ineffective. The use of one drug alone is recommended, where possible, in the management of epilepsy.

Acetaminophen↗
PubMed1977

Interlaboratory variability of valproic acid determinations.

19 pooled plasma specimens were sent as unknowns to 13 participating research laboratories. The interlaboratory variability between the results was very high. Only 4 out of 13 laboratories had 6--12% of their results within the 95% confidence limit for each sample. The precision of repeated determinations was fairly good. 6 out of 10 participating laboratories had a coefficient of variation of less then 5%. The reproducibility and the agreement between the different procedures for quantitative analysis of dipropylacetate is similar to that reported for other major antiepileptic drugs.

Laboratories↗
PubMed1975

Controlled trial of sodium valproate in severe epilepsy.

In a double-blind crossover trial sodium valproate or placebo was added to the existing anticonvulsant treatment of 20 patients with chronic uncontrolled epilepsy. Sodium valproate 1200 mg/day significantly reduced the frequency of both tonic-clonic and minor seizures in these patients. Only mild and transient side effects occurred (drowsiness, ataxia, and nausea), and these may have been due to the effect of adding sodium valproate to existing phenobarbitone or phenytoin treatment. Further controlled trials are needed to assess more fully the efficacy of this drug in various types of epilepsy.

Adult↗
PubMed1975

Brain concentrations of phenytoin, phenobarbitone and primidone in epileptic patients.

Plasma, brain, lumbar CSF, skeletal muscle, skin and bone concentrations of phenytoin, phenobarbitone and primidone have been measured in specimens from patients undergoing temporal lobectomy for chronic epilepsy. A good correlation was found between the plasma and brain concentrations of each drug. Similarly, a good correlation was found between the plasma and CSF concentrations of each drug. Assuming that CSF is an ultrafiltrate of plasma, the percentage of phenytoin, phenobarbitone and primidone which was unbound in plasma was 10-14%, 43% and 81% respectively. Skeletal muscle concentrations of phenytoin and phenobarbitone and the skin concentration of phenytoin, also correlated with the plasma concentrations, but the remaining tissues did not give significant correlations.

Adolescent↗
PubMed1975

Serum-phenytoin levels in management of epilepsy.

Steady-state serum-phenytoin levels were measured in five patients whose phenytoin dosage was changed three or more times for therapeutic purposes. Data from four of these patients and from fifteen others have been used to construct a nomogram which permits the clinician, given a single, accurate, steady-state phenytoin level, to adjust the dosage to achieve the desirable therapeutic concentration of 60 or 80 mumol per litre (15 or 20 mug. per ml.).

Dose-Response Relationship, Drug↗
PubMed1975

Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients.

1 Steady-state serum phenytoin concentrations were measured in adult epileptic patients receiving a maintenance dose of phenytoin (300 mg daily). 2 Serum phenytoin concentration showed a positive correlation with age. 3 Serum phenytoin concentration showed a negative correlation with body weight and with height. Multiple correlation analysis indicated that body weight influenced the concentration to a much greater degree than height. 4 When corrected for body weight and height, the serum phenytoin concentrations in women were lower than those in men, although the difference was not statistically significant. 5 Although each of these factors contributes to the interindividual variation in serum phenytoin concentrations, the contribution of each is small. Other factors, such as genetic differences and the effect of saturation kinetics, are much more important in determining steady-state concentrations. Adjusting the dose according to the age, weight and height of a patient would achieve only a marginal improvement in therapy.

Adult↗
PubMed1975

A study of the pharmacokinetics of phenytoin (diphenylhydantoin) in epileptic patients, and the development of a nomogram for making dose increments.

Phenytoin is metabolized to its parahydroxylated derivative by hepatic microsomal enzymes. This hydroxylation is a saturable process, that is, the rate of metabolism fails to increase in proportion to the serum concentration. This leads to a nonlinear relationship between the maintenance dose of the drug and the resulting steady-state serum level. As the therapeutic range of serum levels is reached, the increase in level produced by a given increment in dose becomes progressively greater. An increment of only 50-100 mg will carry the serum level from the lower to the upper limit of the therapeutic range in most patients. Thus, problems in bioavailability, noncompliance, and drug interactions are an important practical problem with this drug. Monitoring serum phenytoin levels during chronic therapy is an invaluable therapeutic aid, enabling dosage adjustments to be made in order to achieve a level within the therapeutic range. A nomogram is presented in this paper in order to assist the physician in making dosage increments.

Adolescent↗
PubMed1975

Involuntary movements caused by phenytoin intoxication in epileptic patients.

The case histories of four patients who developed choreoathetoid movements during intoxication with phenytoin are presented. Drug intoxication was confirmed in each case by measuring the serum phenytoin concentration. Drug interactions were, in part, responsible for the occurrence of intoxication in three of them. Phenytoin intoxication is not always easy to recognize, particularly when nystagmus is minimal or absent, as in these four patients. The estimation of the serum phenytoin concentration is invaluable in this situation.

Adult↗
PubMed1975

Inhibition of phenytoin metabolism by other drugs used in epilepsy.

Phenytoin metabolism is saturable within its normal therapeutic range and, therefore, small changes in the activity of the enzyme can lead to marked changes in serum phenytoin concentrations. The anticonvulsant drugs sulthiame and pheneturide both inhibit the metabolism of phenytoin. The mechanism of this interaction appears to be different for these two drugs. Nortriptyline produces a small increase in serum phenytoin concentrations, but this is unlikely to be of clinical importance. Case reports suggest that both chlorpromazine and chloramphenicol inhibit phenytoin metabolism to a significant degree.

Adult↗