Does carbamazepine-epoxide conjugate with glutathione? On an existing but almost forgotten possibility.

The anticonvulsant carbamazepine is widely used to treat affective disorders and behavioural disorders in non-epileptic children. We report an elevated plasma level of carbamazepine-10,11-epoxide in a cystinuric child after daily medication with 300 mg carbamazepine while the serum level of carbamazepine was in the therapeutic range. The concentrations of carbamazepine and its epoxide derivative were determined by HPLC. The formation of a glutathione conjugate of carbamazepine-10,11-epoxide is raised as a hypothesis.

Disabling erratic myoclonus during lamotrigine therapy with high serum level--report of two cases.

We present two patients with epilepsy who experienced disabling myoclonic jerks during lamotrigine treatment. Both were young males who had intractable cryptogenic generalized epilepsy since childhood. They received a lamotrigine-valproate combination resulting in an excellent improvement; however, after 2-3 years of therapy, both patients were hospitalized because of continuous disabling myoclonic jerks. The dosage of lamotrigine was the same before and at the onset of myoclonus. When the severe myoclonus started, both patients had a higher serum lamotrigine level (16.5 and 17.7 mg/L, respectively) than in previous findings. Disabling myoclonus was also present during lamotrigine monotherapy with 15 mg/L serum level. Lamotrigine may severely worsen myoclonic phenomena in generalized epilepsies, in which adverse events may be dependent on drug serum level.

[Monitoring of diazepam treatment: comparison of the results of gas chromatography and radioreceptor methods]. / Monitorowane leczenie diazepamem: porównanie wyników uzyskanych metoda chromatografii gazowej i radioreceptorowa.

26 patients with generalized anxiety disorder have been treated with diazepam (20 mg/24h) for 3 weeks. Blood samples were taken on the days of clinical assessment (before treatment and on the 7th, 14th, 21st day). Determination of drug level was performed parallelly by RRA and GC. The results obtained by both methods agreed well. The intra- and interindividual variations were high. We conclude that diazepam can adequately be measured by both techniques.

Neuroendocrine response to clomipramine and desipramine--the evidence of partial determination by heredity and sex.

A single dose of clomipramine, 10 mg i.v., or desipramine, 25 mg i.m., was administered to seven healthy young sibling pairs in a randomized cross-over experiment. The response of serum growth hormone, prolactin and cortisol was measured. The main findings were (1) sex differences in the growth hormone and cortisol response to desipramine and (2) a significant genetic component of the prolactin and cortisol response to desipramine as indicated by significantly (p less than 0.05) lower within-pair than between-pair variance in the sibling pairs but not random pairs of the experimental subjects.

Determination of fluperlapine in human plasma by capillary gas chromatography.

A sensitive and simple gas chromatographic method was developed for the determination of fluperlapine in human blood plasma using amitriptyline as an internal standard. The compounds were extracted into diethyl ether, the extract chromatographed on a dimethyl silicone capillary column, and detected by nitrogen phosphorus selective flame ionization detector. The NP-FID responses, as peak area ratios of the compound and internal standard, were linearly correlated to their plasma concentrations between 10 and 1000 ng/ml. The limit of detection in plasma was 0.5 ng/ml. The relative recovery of fluperlapine was about 85%.

Gas chromatographic method for determination of a piperazine derivative (Trelibet) and its metabolites in human plasma and urine.

A sensitive gas chromatographic method was developed for the determination of Trelibet, 1-benzyl-4-(2'-pyridinecarbonyl)piperazine, and of its major metabolites in biological fluids. The compounds were extracted as bases into dichloromethane, and the extracts were analysed by a dimethylsilicone capillary column with a nitrogen-phosphorus flame-ionization detector. The lower limit of detection was 1 ng/ml for Trelibet and 5 ng/ml for the metabolites. Peak-area ratios of the compounds and internal standard were linearly correlated to their plasma concentrations between 1 and 1000 ng/ml. The method was used for quantification of Trelibet and two of its metabolites in depressed patients after oral administration of a single dose of 200 mg of Trelibet. Concentration data measured in plasma and urine showed that the method is sensitive enough to monitor concentrations both for pharmacokinetic studies and for plasma steady-state levels daily.