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Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

At least 181 records · Page 10Linked to original sources
PubMed1980

The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy.

In a group of 5 women on long-term anticonvulsant and oral contraceptive therapy, the plasma ethynylestradiol (EE) concentration on 50 microgram EE daily was 11.1 +/- 4.5 pg/ml. These values were at the lower end of the range found in normal women in this laboratory taking 30 microgram EE daily (6-190 pg/ml). Four women have been studied prospectively for 3 months, over 1 cycle before and 2 cycles during phenobarbital 30 mg b.i.d. therapy. Significant falls in the plasma EE concentration were seen in two women (from 104.8 +/- 13.4 to 37.7 +/- 2.0 pg/ml and from 125.6 +/- 23.8 to 34.8 +/- 6.7 pg/ml p less than 0.01) and breakthrough bleeding was seen in both women. No changes in plasma concentrations of follicle stimulating hormone, progesterone, norethindrone or norgestrel were seen. There was a significant increase in the sex hormone binding globulin capacity from 100.7 +/- 5.8 to 133.3 +/- 1.2 nmoles/1 (p less than 0.05). These changes are consistent with the known microsomal enzyme inducing effect of phenobarbital.

Adolescent↗
PubMed1980

Effect of single doses of sodium valproate on serum phenytoin levels and protein binding in epileptic patients.

Our study underlines the importance of performing protein binding interaction studies in vivo. Predictions from in vitro studies may be misleading because they may not take into account the kinetics of the drug in the whole animal. Probably the most important clinical implication of these findings is that total serum phenytoin levels may fall when sodium valproate is added to therapy and this may lead to an increase in dose under the mistaken belief that the effect of the drug has been reduced. Since it is the bound and not the free drug which is reduced, phenytoin intoxication may result from this misguided action.

Adult↗
PubMed1980

Quality control in drug measurement.

Therapeutic drug monitoring of serum concentrations has become a rapidly expanding area of clinical pharmacology and is likely to remain an important growth area in the future, despite that the evidence for the efficacy of such monitoring is inconclusive except for a handful of drugs and findings that the reliability of much drug assay work is far from optimal. Nonetheless, in view of the likelihood that the use of routine monitoring will increase, the institution of quality control programs seems not only desirable, but necessary. We describe the design of Bartscontrol (formerly known as St. Bartholomew's Hospital Quality Control Scheme for Antiepileptic Drugs) and discuss the experience of this program. Although the feedback provided to the participants of such a program seems to encourage an overall increase in precision, our findings also indicate that some laboratories perform consistently badly. While the data generally do not reveal that variations in precision are due to analytical method employed, a scheme such as the one described can occasionally make the important finding that a particular technique is inappropriate, as was found for the case of spectrophotometry for phenytoin.

Anticonvulsants↗
PubMed1980

A comparative study of antipyrine and lignocaine disposition in normal subjects and in patients treated with enzyme-inducing drugs.

1 The disposition kinetics of lignocaine and antipyrine were compared in eight normal subjects and in eleven patients receiving chronic therapy with antiepileptic drugs. The urinary excretion of D-glucaric acid (D-GA) was measured in 16 subjects. 2 In patients treated with antiepileptic drugs antipyrine clearance and D-GA excretion were significantly increased, whereas lignocaine biovailability was significantly reduced. 3 When all the subjects included in the study were considered, a significant positive correlation could be found between the apparent oral clearance of lignocaine (Dose/area under the blood concentration curve) and both antipyrine clearance (r = 0.73) and D-GA excretion (r = 0.74). 4 When normal subjects and epileptic patients were considered separately, a significant positive correlation could be confirmed between the apparent oral clearance of lignocaine and both antipyrine clearance (r = 0.71) and D-GA excretion (r = 0.76) in normal subjects, and between antipyrine clearance and D-GA excretion (r = 0.75) in epileptic patients. 5 These results suggest that the reduction of the oral availability of lignocaine in epileptic patients is secondary to induction of first-pass metabolism of the latter drug.

Adolescent↗
PubMed1980

Quantitative assessment of smooth-pursuit eye movements in healthy and epileptic subjects.

A quantitative electro-oculographic method was used to assess the impairment in smooth-pursuit and vestibulo-ocular reflex suppression eye movements in 12 epileptic patients and eight normal volunteers. Both types of eye movement were impaired by a factor of 40% in the epileptic patients, and the impairment was at least partly due to the treatment with phenytoin and phenobarbitone. There was a strong positive correlation between the performances in vestibulo-ocular reflex suppression and smooth-pursuit.

Adolescent↗
PubMed1980

Reversal by phenytoin of carbamazepine-induced water intoxication: a pharmacokinetic interaction.

The hypothesis that phenytoin may antagonise the antidiuretic effect of carbamazepine has been examined by comparing the free water clearance response to a standard water load in 36 patients stabilised on different drug regimes. The diuretic response to the water load was significantly greater in patients receiving chronic treatment with carbamazepine and phenytoin in combination than in matched control subjects receiving carbamazepine as a single drug. Acute administration of phenytoin (1,100 mg), however, had no significant influence on carbamazepine-induced antidiuresis. Evidence is presented that reversal of the antidiuretic effect of carbamazepine by chronic phenytoin administration is secondary to a marked reduction of the serum carbamazepine concentration during combined therapy. These results suggest that the risk of developing water intoxication is greater in patients receiving carbamazepine alone than in those receiving phenytoin in combination. Since the antidiuretic effect is correlated with the serum carbamazepine concentration rather than with the prescribed daily dose, monitoring the serum level of the drug is likely to provide the best rational approach to the prevention of excessive water retention.

Adult↗
PubMed1980

Effects of sodium valproate on the serum protein binding of phenytoin, and on liver enzyme activity.

The effect of a single dose of sodium valproate on the serum protein binding of phenytoin was studied in 6 epileptic patients receiving phenytoin maintenance therapy. Phenytoin was significantly displaced by valproic acid, but the free concentration of phenytoin was unchanged because of redistribution to tissues. As a result of this effect, total serum phenytoin concentration was significantly lowered. Induction of metabolism probably does not play a part in this interaction because antipyrine half-lives and urinary D-glucaric acid excretion were not altered by chronic administration of sodium valproate to 8 patients receiving this drug alone.

Antipyrine↗
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↗