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Biomedical subjects

A Richens

Publications and source records attributed to A Richens.

260 records · Page 15Linked to original sources
PubMedDate not supplied

The clinical value of serum prolactin measurement in the differential diagnosis of complex partial seizures.

The time course of changes in serum prolactin after complex partial seizures has been determined and compared to similar changes after other types of seizure and non-epileptic attacks. Seizures in 33 subjects were recorded on video EEG telemetry. Peak serum prolactin concentrations occurred 15-20 min after tonic-clonic seizures, 10 min after complex partial seizures, and were highest after generalised tonic-clonic seizures. Serum prolactin concentrations remained less than 1000 mU/l after absences and non-epileptic attacks. Application of Bayes' theorem showed that where serum prolactin was greater than 1000 mU/l 5-10 min post event this would identify genuine tonic-clonic or complex partial seizures. The false negative rate of this test was 9% for tonic-clonic seizures and 38% for complex partial seizures. Failure of serum prolactin to rise after an attack is of little value in distinguishing complex partial seizures from non-epileptic attacks.

Adolescent↗
PubMedDate not supplied

Controlled trial of lamotrigine (Lamictal) for refractory partial seizures.

The antiepileptic effect of lamotrigine (LTG) was assessed in a double-blind, placebo-controlled crossover trial in 24 adult patients with refractory partial seizures. LTG or placebo was added to existing antiepileptic drugs (AEDs). The dose of LTG varied from 75 to 400 mg daily. Three patients did not complete the trial. One was withdrawn from the trial with ataxia, tiredness, dyspnea, and diplopia while receiving LTG and died 18 days later of invasive carcinoma involving the liver. A second patient was withdrawn during baseline for contravening admission criteria, and a third received LTG in error during both treatment periods. Twenty-one patients (12 men and 9 women) completed the trial. An analysis of seizure counts in the 12-week treatment period with LTG showed a statistically significant reduction in seizures as compared with placebo for total seizures (p less than 0.002), partial seizures (p less than 0.002), and secondarily generalized seizures (p less than 0.05). The analysis of total seizure days showed a significant reduction during LTG treatment (p less than 0.002). There were no statistically significant changes in plasma concentrations of phenytoin (PHT), carbamazepine (CBZ), primidone (PRM), or phenobarbital (PB) between the two treatment periods. The most common adverse events reported during the trial were diplopia, drowsiness, tiredness, ataxia, and headache, but although these were more frequent during LTG treatment, the differences from placebo were not statistically significant. No hematological or biochemical changes were noted.

Adolescent↗
PubMedDate not supplied

Clinical pharmacokinetics of phenytoin.

Phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt. Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in Scandinavia. The drug has a moderately large volume of distribution and is approximately 90% bound to plasma proteins. Clinically important displacement can be caused by bilirubin and several drugs, particularly sodium valproate, which is often combined with phenytoin. Displacement will lower the total serum concentration but will little affect the free drug concentration. The metabolism of phenytoin to the major metabolite, 5-(p-hydroxyphenyl)-5-(phenylhydantoin, is saturable, giving rise to a non linear dose-serum concentration relationship. Therefore, the dose range compatible with a therapeutic serum concentration is narrow within subjects, and monitoring serum concentrations is of particular value in dosage tailoring. In renal failure, the binding of phenytoin to plasma proteins is reduced and therefore a lower range of serum drug concentrations is compatible with therapeutic control. In liver disease, binding may also be impaired but delayed metabolism may occur in addition. During pregnancy the serum concentration may fall progressively as pregnancy advances, probably due to an increased rate of metabolism. Phenytoin readily crosses the placenta, and is metabolised rapidly by the neonate exposed in utero.

Aged↗
PubMedDate not supplied

Effect of dose increments on serum carbamazepine concentration in epileptic patients.

The effect of progressive dose increments on the steady-state serum concentration of carbamazepine has been investigated prospectively in 20 adult institutionalised epileptic patients receiving long term therapy with the drug. In all but 1 subject, a strong positive correlation between the serum carbamazepine concentration and the prescribed daily dose was found. The relationship appeared to be linear over the dosage range examined (600 to 1400mg in most patients). In some patients, a trend was observed for the extrapolated regression lines to yield positive y-axis intercepts. The latter were significantly different from zero in 3 patients. Although these findings suggest that the relationship between serum carbamazepine concentration and dose may be curvilinear over the lower range of doses, further studies are required to clarify this point.

Adult↗
PubMedDate not supplied

Quality control of drug assays.

Previously published work relating to quality control of drug assays has dealt mainly with interlaboratory comparisons. It is suggested that participants in external quality assessment schemes wil derive the maximum benefit from their participation if a suitable intralaboratory quality control scheme is established. Such a scheme should be capable of providing estimates of within- and between-batch imprecision over the concentration range for which the assay is used and give an indication of the development of systematic error (relative to previous performance). A scheme using serum pools at 3 concentrations, each to be analysed at least in duplicate, is recommended. Adaptations of this scheme, to be used when the number of patient samples per batch does not justify this number of control samples, are discussed in relation to various analytical situations. A ratio of 1 control sample to 10 patient samples is considered reasonable. The interpretation of results from external quality assessment schemes using performance indices, graphical assessment of 'bias' and standard deviation interval (SDI = bias divided by standard deviation) and the statistical evaluation of proportional and additive error by linear regression (least squares) analysis is discussed. In some cases it has been possible, from the results of interlaboratory studies, to show that a particular method will not generally give satisfactory results when compared either with other currently available methods, e.g. UV - spectrophotometric methods for phenobarbitone, phenytoin, carbamazepine and theophylline, or on the grounds of clinical requirements, e.g. doubling dilution broth techniques for gentamicin. Improvement in intralaboratory reproducibility would facilitate the identification of technical factors contributing to interlaboratory variation.

Animals↗
PubMedDate not supplied

Pharmacokinetics of phenylethylmalonamide (PEMA) after oral and intravenous administration.

The pharmacokinetics of phenylethylmalonamide (PEMA), one of the major metabolites of the antiepileptic drug primidone, have been studied in 6 healthy volunteers after administration of single 500mg intravenous and oral doses. Following intravenous administration, after a very short distributive phase (t1/2 = 0.23-0.53h), the decline of the log-PEMA concentration with respect to time appeared linear. The pharmacokinetic parameters, calculated according to a 1-compartment open model, showed the following values (mean +/- SD): terminal half-life, 15.7 +/- 3.4h; apparent volume of distribution, 0.69 +/- 0.10 L/kg; total serum clearance, 31.3 +/- 6.6 ml/h/kg. After oral administration, peak serum concentrations occurred at 0.5 to 4 hours and the oral bioavailability was 86.4 to 95.9%.

Administration, Oral↗
PubMedDate not supplied

Steady-state pharmacokinetics of phenytoin from routinely collected patient data.

Previously reported routine phenytoin clinical pharmacokinetic data from Japan, England, and Germany were analysed to estimate population pharmacokinetic parameters. There were 780 steady-state phenytoin concentrations and associated dosage rates (mg/day) from 322 patients. The patient group spanned paediatric and adult ages, mean age being 18.4 +/- 17.3 (SD) years; 53% were males. The data were analysed using NONMEM, a computer programme designed for population pharmacokinetic analysis. Estimates of the influence of age, gender, data source, height and weight on the maximum elimination rate (Vm) and Michaelis-Menten constant (Km) were obtained. The Vm and Km of a 70 kg adult male European were estimated to be 415 mg/day and 5.7 mg/L, respectively. Vm is not influenced by gender, age or data source. The parameters of a power function of height and weight were estimated to adjust Vm for body size. The best function adjusts Vm in proportion to weight to the 0.6 power; height contains no useful information. Km is not influenced by gender. The Km for patients less than 15 years old is 43% less than that of older patients. The Km of Japanese patients appears to be 23% less than that for European patients. Even after adjustments for age, etc., apparent Vm and Km vary unpredictably among individuals with a coefficient of variation between 10 to 20% and approximately 50% respectively.

Adolescent↗