1. Inter‐ and intrasubject variability in the gastric emptying of semisolids and liquids was measured by scintigraphic emptying of radionuclide‐labelled semisolid and from paracetamol absorption in ten healthy volunteers of both sexes. 2. The intrasubject variability was not statistically significant for any of scintigraphic or paracetamol absorption parameters. 3. The intersubject variation was significant for all scintigraphic and paracetamol absorption parameters. 4. In women, the gastric emptying rate of semisolid decreased linearly during the menstrual cycle. 5. The lag period and paracetamol absorption parameters were unrelated to the day of the menstrual cycle day. 6. There was no statistically significant relationship between scintigraphic and paracetamol absorption parameters.

Summary The antiepileptic effect of valproate sodium (VPA) versus that of placebo has been evaluated in a controlled clinical trial (double‐blind, crossover type). The concentration of VPA and that of other antiepileptic drugs in serum, as well as findings by EEG, were recorded in the course of the trial. When VPA was added to the conventional antiepileptic treatment, which preferably was maintained constant, the frequency of seizures was significantly reduced in 21 patients (60%); it remained unchanged in 7 (20%), and increased in 7 (20%). No correlation between a reduced frequency of seizures and the concentration of VPA in serum was observed. Nor was there any significant correlation between the clinical and the EEG ratings of the therapeutic effect. The adverse reaction most commonly encountered was fatigue associated with hypersalivation. Alopecia developed in 2 patients. When VPA was administered together with phenobarbital, the dose of the latter had to be reduced by approximately 30% if the serum concentration of phenobarbital was to be maintained at a constant level. When patients were treated with phenytoin, additional d o s e s of VPA brought about a decrease in the serum concentration of phenytoin even though doses remained unchanged. RÉSUMÉ On a øvalué l'action antiépileptique du sodium valproate (VPA) par rapport a Paction d'un placébo dans une étude contrôlée (en double‐aveugle). On a pris en considération les taux de VPA et ceux des autres drogues antiépileptiques et les données EEG. Si on ajoute du VPA à un traitement antépileptique de préférence inchingé il y a une réduction des crises, significative chez 21 sujets (60%) pas de modification chez 7 (20%), et une augmentation des crises chez 7 (20%). Il n'y avait pas de corrélation entre la diminution des crises et les taux sériques de VPA et entre les effets cliniques et les donndée EEG. Les effets fré‐quemment observés étaient une fatigabilityé et une hypersalivation; une alopécie est survenue chez deux patients. Si on administrait du VPA avec du phénobarbital, la dose de ce dernier devait être réduite d'environ 30% pour le garder dans des taux sériques constants. Si les patients étaient en traitement avec de la diphénylhydantoine l'addition de VPA deaterminait une diminution des taux de DPH. RESUMEN En un ensayo chínico controlado (tipo doble ciego crossover) se han valorado los efectos antiepilépticos del valproato sódico (di‐n‐propilacetato sódico, VPA) compareándolos con placebo. En el transcurso del ensayo se anotaron las concentraciones en suero de VPA y otros antiepilépticos a la vez que los hallazgos del EEG. Si el VPA se añadia al tratamiento anticonvulsive convencional, que se mantuvo constante, se re‐dujo significativamente la frecuencia de los ataques en 21 enfermos (60%), no se modificó en 7 (20%) y au‐mentó en 7 (20%). No se observó ninguna correlación entre la reducción de la frecuencia de los ataques y la concentración del VPA en suero. No se observó ninguna correlación significativa entre la valoración clínica y electroencefalog...

Clinical effects at three different serum levels of sodium valproate (VPA) were compared in a triple-blind, multiple crossover trial comprising 13 epileptic inpatients. Patients were selected regardless of seizure type, and all were in concomitant antiepileptic treatment, which was kept constant throughout the study. A significant relationship between the decrease in number of seizures and increasing VPA serum level was demonstrated. The relationship between VPA dose and serum level was curvilinear. Statistical evaluation of patients by seizure type in relation to clinical effect of VPA was only possible for secondary generalized seizures. Between phenytoin, phenobarbital, and carbamazepine and the different VPA serum levels no interactions could be demonstrated. Recorded side effects were always mild and transient. No obvious correlation between side effects and VPA serum level was established.

No abstract

1 A sparteine/mephenytoin phenotyping test was carried out in 37 Vietnamese living in Denmark. By visual inspection the urinary S/R-mephenytoin ratio appeared to show a bimodal frequency distribution. Eight putative poor metabolizers of mephenytoin, PMm (22%), had S/R-mephenytoin ratios from 0.79 to 1.12 and 29 putative extensive metabolizers of mephenytoin, EMm, had S/R-mephenytoin ratios S 0.55. All of the subjects were extensive metabolizers of sparteine with urinary metabolic ratios from 0.15 to 2.4. 2 The metabolism of the antimalarial prodrug proguanil was studied in 34 of the subjects after a single oral dose of 100 mg. The median 12 h urinary recoveries of the active metabolite cycloguanil and the minor metabolite 4-chlorphenylbiguanide were 5.8 and 1.9% of the dose, respectively, in 26 EMm compared with 1.6 and 0.4%, respectively, in 8 PMm (P < 0.001, Mann-Whitney U-test).3 There was no statistically significant correlation (Spearmans r,) between any index of proguanil metabolism and the sparteine metabolic ratio.