The effect of cinromide on “kindled” seizures in the rat

Cinromide, an experimental anticonvulsant (Burroughs Wellcome Co.), was tested against focal cortical (simple partial analog), focal amygdala (complex partial analog), and generalized convulsive (tonic-clonic analog) seizures in the “kindled” rat. The toxicity in the CNS was measured by the ataxia scale devised by Desmedt. Niemegeers, Lewi and Janssen (Arzneimittel-Forsch.26: 1592–1602, 1976). Cinromide was found to suppress generalized convulsions in small, subtoxic doses, whereas larger, sometimes toxic doses were required to suppress focal seizure activity. The general pattern of response resembles that of the standard clinical anticonvulsants which the present authors have previously investigated. Cinromide, however, was relatively more potent against focal amygdala (complex partial analog) seizures than any drug previously tested, except carbamazepine. These data suggest that cinromide should be clinically effective, not only against tonic-clonic seizures, but also, toxicity permitting, against complex partial attacks as well.     

Kinetics of phenobarbital in normal subjects and epileptic patients

Summary The kinetics of phenobarbital (PB) were evaluated in six normal subjects and six epileptic patients treated with phenytoin or carbamazepine. Each normal subject received three single doses of PB: PB-sodium 130 mg i.v. (IV), PB sodium 130 mg i.m. (IM), and PB acid 100 mg orally (PO), in random order at least one month apart. After IV PB distributive half-lives varied from 0.13 to 0.70 h, disposition half-lives were 75 to 126 h, steady state volume of distribution (V_ss) was 0.54±0.03 l/kg, and clearance (CL) was 3.8±0.77 ml/h/kg. Absolute bioavailability of IM PB was 101±13%, of PO PB (corrected for dose) 100±11%. Peak serum PB concentrations were achieved from 2 to 8 h after IM administration, and from 0.5 to 4 h after PO administration. Epileptic patients exhibited similar PB kinetics: disposition half-lives were 77 to 128 h, V_ss 0.61±0.05 l/kg, and Cl 3.9±0.76 ml/h/kg. Phenobarbital appears to represent an exception among antiepileptic drugs, in that pharmacokinetic data obtained in normals can reasonably be extrapolated to the epileptic population.     

Single-dose and steady-state kinetics of morphine and its metabolites in cancer patients — a comparison of two oral formulations

Summary The single-dose and steady state kinetics of morphine given as controlled-release tablets (30 mg every 12 h) and as a solution (15 mg every 6 h) have been compared in 11 cancer patients with chronic pain. The concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were analyzed by HPLC.There were no significant differences between the tablets and solution in the mean steady state concentrations of morphine, M3G or M6G. The t_max was 3.3 h for the tablets compared to 1.1 h for the solution.After giving the controlled-release tablets every 12 h there was a significantly higher fluctuation index of the morphine concentrations than after the solution. Urinary recovery at steady state was comparable between the two preparations, with averages of 57% and 47%, respectively.Thus, no major differences were found in the pharmacokinetics of morphine and its glucuronidated metabolites after 30 mg morphine as controlled-release tablets every 12 h or 15 mg of morphine solution every 6 h, except for a significantly longer t_max and greater fluctuation in morphine concentrations after the controlled-release tablets.     

Fractions metabolized in a triangular metabolic system: Cinromide and two metabolites in the rhesus monkey

A previous study of the metabolic fate of cinromide (3-bromo-N-ethylcinnamamide) in rhesus monkey established that half of a dose is metabolized byN-deethylation to an active metabolite, 3-bromocinnamamide. Both cinromide and its proximal metabolite can be metabolized by amide hydrolysis to a second metabolite, 3-bromocinnamic acid, resulting in a triangular metabolic problem. This investigation was undertaken to distinguish between these two nonexclusive possibilites. A preliminary study was carried out to characterize the pharmacokinetics of 3-bromocinnamic acid. In the main study, six monkeys received an intravenous dose of cinromide, 3-bromocinnamamide, and 3-bromocinnamic acid in a randomized order. The time courses of compound administered and corresponding metabolites were followed. The following fractions of dose metabolized (mean±SD) were obtained: cinromide to 3-bromocinnamide: 0.53 ±0.24; 3-bromocinnamamide to 3-bromocinnamic acid: 0.53 ±0.21; cinromide to 3-bromocinnamic acid directly: 0.48 ±0.32. Thus, it was found that 3-bromocinnamic acid is formed directly from cinromide and from 3-bromocinnamamide. Also, as primary metabolites, 3-bromocinnamic acid and 3-bromocinamamide account for all of a cinromide dose with a mean value of 1.00±0.34. The observed variability in these fractions metabolized was explained by the fact that in the solution of the triangular metabolic problem, three clearances are assumed to remain constant over three studies.This paper represents #2 in the series of Pharmacokinetic Relationships of Cinromide and its Metabolites in Rhesus Monkey. Supported in part by National Institutes of Health contract NO1-NS-1-2282.     

癫痫患者血清催乳素的检测及其临床意义

目的 :为了研究癫痫患者下丘脑功能的改变及催乳素 ( PRL)在癫痫诊断中的临床意义。方法 :选择了 2 7例癫痫患者 ,2 5例非癫痫患者及 30例正常人作为对照组 ,分别采集其血样 ,用放射免疫法检测血清 PRL水平的变化。结果 :癫痫患者血清 PRL 水平明显高于非癫痫组及对照组 ,非癫痫组与对照组之间差异无显著性。结论 :癫痫发作对下丘脑 -垂体轴有一定影响 ,血清 PRL 升高的比率可作为癫痫鉴别诊断的一个参考指标     

Multiple dose kinetics of ofloxacin and ofloxacin metabolites in haemodialysis patients

Summary 7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC.Peak (3.1 mg·1^–1) and trough levels (1.6 mg·1^–1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t_1/2) and during the haemodialysis session (t_1/2HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml·min^–1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t_1/2 of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively.It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.     

Doxepin and its metabolites in plasma and cerebrospinal fluid in depressed patients

Little information exists on the concentrations of antidepressants and their metabolites in CSF. We measured plasma and CSF levels of trans-doxepin (trans-DOX) and DOX metabolites in 12 depressed patients treated with DOX (250 mg/day) for 6 days. Spinal taps and blood samples were taken on day 7, 10 h after drug administration. Trans-DOX, cis-desmethyldoxepin (cis-DM-DOX), trans-desmethyldoxepin (trans-DM-DOX) and di-desmethyldoxepin (DDM-DOX) were analyzed in CSF and plasma samples by HPLC with column-switching. Although DOX was given as a mixture of 85% trans-DOX and 15% of the pharmacologically more active cis-DOX, we found similar amounts of cis-DM-DOX and trans-DM-DOX in plasma (59.8 ± 45.1 versus 72.0 ± 60.0 ng/ml; NS), suggesting that isomerization of DOX had taken place. Trans-DOX and DOX metabolites could be detected in CSF of most patients. Relatively low CSF concentrations of the active metabolite cis-DM-DOX were measured. Clinical efficacy, as assessed by HAMD scores, was not significantly related to plasma or CSF concentrations of trans-DOX or its metabolites. Trans-DOX and DOX metabolites were distributed differently between plasma and CSF. It is concluded that isomerization of DOX is not only relevant for neuronal uptake inhibition, but also for the transport of the metabolites. Received: 13 May 1996/Final version: 16 December 1996     

Fractions metabolized in a triangular metabolic system: cinromide and two metabolites in the rhesus monkey

A previous study of the metabolic fate of cinromide (3-bromo-N-ethylcinnamamide) in rhesus monkey established that half of a dose is metabolized by N-deethylation to an active metabolite, 3-bromocinnamamide. Both cinromide and its proximal metabolite can be metabolized by amide hydrolysis to a second metabolite, 3-bromocinnamic acid, resulting in a triangular metabolic problem. This investigation was undertaken to distinguish between these two nonexclusive possibilites. A preliminary study was carried out to characterize the pharmacokinetics of 3-bromocinnamic acid. In the main study, six monkeys received an intravenous dose of cinromide, 3-bromocinnamamide, and 3-bromocinnamic acid in a randomized order. The time courses of compound administered and corresponding metabolites were followed. The following fractions of dose metabolized (mean +/- SD) were obtained: cinromide to 3-bromocinnamide: 0.53 +/- 0.24; 3-bromocinnamamide to 3-bromocinnamic acid: 0.53 +/- 0.21; cinromide to 3-bromocinnamic acid directly: 0.48 +/- 0.32. Thus, it was found that 3-bromocinnamic acid is formed directly from cinromide and from 3-bromocinnamamide. Also, as primary metabolites, 3-bromocinnamic acid and 3-bromocinamamide account for all of a cinromide dose with a mean value of 1.00 +/- 0.34. The observed variability in these fractions metabolized was explained by the fact that in the solution of the triangular metabolic problem, three clearances are assumed to remain constant over three studies.     

Gender differences in plasma clozapine levels and its metabolites in schizophrenic patients

Forty refractory schizophrenic patients (21 females and 19 males) participated in a fixed-dose study with clozapine. After a 6-week trial of haloperidol and a 1-week washout time period, non-responding patients were placed on clozapine and the dosage titrated up to 400 mg/day for the next 5 weeks. Plasma clozapine levels and its two metabolites desmethylclozapine (DCLOZ) and clozapine N-oxide (CNO) were measured at weeks 2, 4 and 6. Blood samples were obtained 10–12 h post-evening dose and prior to the morning dose. Clozapine and its metabolites were assayed by HPLC with UV detection. Patients were assessed for clinical response with the Brief Psychiatric Rating Scale (BPRS) at baseline and at weeks 2, 4 and 6. BPRS scores were also divided into positive (+) and negative (−) symptoms subscales. Plasma clozapine and DCLOZ levels were significantly lower in males. Plasma CNO levels were slightly lower in males but it was not statistically significant. Decreased total BPRS, (+) and (−) symptoms subscale scores occurred during the study for both gender groups. A greater magnitude of change for the (−) symptom subscale score was observed in the male group. Gender was not a significant factor in the incidence or severity of side-effects. © 1997 John Wiley & Sons, Ltd.     

Concentrations of chlorpromazine and two of its active metabolites in plasma and cerebrospinal fluid of psychotic patients treated with fixed drug doses

Efforts to find a correlation between serum levels of chlorpromazine (CPZ) and clinical effect have been rather unsuccessful, which could be due to fluctuations of CPZ and CPZ metabolite levels during treatment, the complicated metabolism of CPZ, or to varying degrees of protein binding. Using a mass fragmentographic analysis technique the variations of CPZ and two active metabolites nor₁-CPZ and 7-OH-CPZ were studied in ten schizophrenic patients during the day at steady state and after withdrawal.There was a significant correlation between the area under curve (AUC) for CPZ in serum during 24-h treatment and serum concentration at different fixed times of the day. The half-life (T _1/2) for CPZ was found to be 8–33h. 7-OH-CPZ and nor₁-CPZ disappeared at about the same rate as the parent compound. The concentration of both metabolites was less than 10 ng/ml after 36 h.CPZ was administered to 43 schizophrenic patients in one of three fixed doses (200, 400, or 600 mg) according to a double-blind design. Plasma and cerebrospinal fluid (CSF) samples were analysed before and after both 2 and 4 weeks' treatment. The levels of the metabolites were considerably lower as compared to CPZ levels. The same levels were found after 2 and 4 weeks' treatment. There were no sex differences.The levels of CPZ and metabolites presented a weak positive correlation to daily dose but not to dose calculated by mg/kg body weight. Older patients tended to have higher CPZ and metabolite levels. The dose effects were very similar in plasma and CSF and there was a highly significant correlation between CPZ levels in serum and CSF. CSF/plasma ratio for CPZ seems to be an individual factor possibly related to variations in protein-binding in plasma and CSF.     

Cerebrospinal fluid concentrations of thioridazine and its main metabolites in psychiatric patients

Summary A gas chromatographic method for the determination of thioridazine and its metabolites has been developed for assay of the very low concentrations of these substances in the CSF. A certain degree of protein-binding in CSF was demonstrated by equilibrium dialysis, particularly of thioridazine, and to a lesser degree of its metabolites. In 48 psychiatric patients treated with thioridazine, 40 to 1000 mg/day, the mean total concentration of thioridazine in the CSF was 19.4 nmoles/l (range 4.0–47.3 nmoles/l), of thioridazine side-chain sulfoxide 30.5 nmoles/l (range 7.3–109.4 nmoles/l), of thioridazine side-chain sulfone 8.4 nmoles/l (range 1.4–19.6 nmoles/l), and of thioridazine ring sulfoxide 27.7 nmoles/l (range 4.0–71.0 nmoles/l). The free fraction of thioridazine in CSF averaged 49.1% (range 22.4–80.9%), and the corresponding values for thioridazine side-chain sulfoxide were 92% (range 72.5–109.7%) for thioridazine side-chain sulfone 68.8% (range 28.4–98.0%), and for thioridazine ring sulfoxide 81.7% (range 31.0–106.2%). The total CSF concentrations of thioridazine and thioridazine side-chain sulfone were significantly higher than their free serum concentrations whereas the total CSF concentration of thioridazine ring sulfoxide was significantly lower than its unbound serum concentration, and the total CSF concentration of the thioridazine side-chain sulfoxide did not differ from its free serum concentration. The unbound CSF concentration of thioridazine was also significantly higher than its unbound serum concentration (average 1.98 times higher; range 1.37–3.53). The unbound CSF concentration of the ring sulfoxide was only 43% (range 28–61%) of its unbound serum concentration (p <0.008), and the unbound concentrations of the other metabolites did not differ significantly between CSF and serum. Both the total and free CSF concentrations of thioridazine and its metabolites showed positive and usually quite significant correlations with the corresponding unbound concentrations in serum. The concentrations in CSF were much more closely related to the serum concentration than to the dose of thioridazine. The ratio of the total CSF concentration and the unbound serum concentration of thioridazine varied closely with the total CSF protein and albumin concentrations, but the ratio of the unbound CSF and serum concentrations did not show such a covariation. The concentrations of thioridazine in serum and CSF varied significantly with the age of the patients, but no other correlation with age could be demonstrated in the drug-related parameters. The sex of the patients appeared to influence the side-chain oxidation products, as the total CSF concentrations of the thioridazine side-chain sulfoxide and side-chain sulfone, as well as the free fraction in CSF of thioridazine side-chain sulfoxide, were significantly higher in women.     

Pharmacokinetics of ketamine and two metabolites in the dog

The plasma concentrations of ketamine, N-demethylketamine (I), and the cyclohexene metabolite (II) formed by oxidation of I were determined at various times after rapid i.v. administration of 15 mg of ketamine HCl/kg of body weight to dogs. A pharmacokinetic model that included two compartments for ketamine and one compartment for each metabolite was developed. Ketamine distributed rapidly with (t _1/2 averaging 1.95 min. The apparent volumes of the central and peripheral compartments for ketamine averaged 542 and 1940 ml/kg of body weight, respectively, and the (t _1/2 ) averaged 61 min. The model indicated that 62% of ketamine was transformed to I and that 11% of I was converted to II. The apparent volumes of distribution of I and II averaged 61% and 59% of body weight, respectively. The total body clearances (plasma) of ketamine, I, and II averaged 32.2, 89.4, and 8.54 ml/min/kg, respectively. Plasma protein binding was determined by equilibrium dialysis; it averaged 53.5% for ketamine (concentration range 0.34– 19.5 g/ml), 60.3% for I (0.05– 19.6 g/ml), and 70.1% for II (0.09– 0.58 g/ml). A minimum anesthetic concentration of 3 g ketamine HCl/ml plasma was used with the model to predict that the duration of ketamine anesthesia after an i.m. dose would not be significantly affected if the absorption t_1/2 varied from 0.48 to 31 min. The model also predicted that accumulation of I and II would not interfere with ketamine anesthesia that was prolonged by repeated doses, each dose administered i.v. on termination of anesthesia from the previous dose.     

Thyroid hormone concentrations in epileptic patients

Summary Anticonvulsants are associated with decreased serum thyroid hormone concentrations. We have studied thyroid function in 54 epileptic patients on a variety of drugs (19 on carbamazepine, 13 on phenytoin, 10 on sodium valproate, 12 on polypharmacy). For comparison, 14 untreated epileptics and 11 healthy unmedicated volunteers were included as controls.Total thyroxine (T₄) concentrations were reduced in patients taking enzyme-inducing drugs (carbamazepine and/or phenytoin) compared with both controls and patients taking sodium valproate. Similar differences were shown with each individual drug. All nine patients whose circulating T₄ was below the lower limit of the reference range were taking enzyme inducers. Free thyroxine concentrations were also reduced in individuals treated with carbamazepine and phenytoin with five values falling beneath the reference range. Tri-iodothyronine and thyrotropin appeared unaffected by anticonvulsant administration. Thyrotropin releasing hormone stimulation revealed no true hypothyroidism.The lowering effect of anticonvulsant drugs on circulating total and free T₄ was not exhibited by the non-inducing sodium valproate. These data support the influence of enzyme induction as a likely mechanism for reduced thyroxine concentrations in treated epileptic patients.     

Central excitatory properties of Δ9-tetrahydrocannabinol and its metabolites in iron-induced epileptic rats

The effects of δ⁹-tetrahydrocannabinol (Δ⁹-THC), two of its metabolites, 8β-hydroxy-Δ⁹-THC and 11-hydroxy-Δ⁹-THC, and cannabidiol were comparatively studied by means of an iron-induced cortical focal epilepsy in conscious rats with chronically implanted electrodes. Δ⁹-Tetrahydrocannabinol produced depression of the spontaneously firing epileptic focus, excitatory behavior, generalized after-discharge-like bursts of epileptiform polyspikes and frank convulsions. The pharmacological profiles of the two metabolites differed from that of the parent compound: 11-Hydroxy-Δ⁹-THC did not precipitate convulsions, but it did elicit all the other effects of Δ⁹-THC; the 8β-hydroxy derivative, on the other hand, exerted only two Δ⁹-THC-like effects; that is, it evoked polyspike bursts and convulsions. In contrast, cannabidiol, even in large doses (100 mg/kg) was devoid of all the effects of Δ⁹-THC. Furthermore, pretreatment with cannabidiol markedly altered the responses to Δ⁹-THC in the following ways: focal depression was partially blocked, polyspike activity was enhanced and convulsions abolished. Phenytoin pretreatment elicited similar effects, but it failed to block the Δ⁹-THC-induced convulsions. In general, the cannabinoids exhibit a wide spectrum of CNS effects ranging from focal depression to convulsions; specifically, however, the pharmacological profile of each agent can differ markedly; for example, the convulsant properties of Δ⁹-THC are not a universal characteristic of this class of drugs.     

Presence of chlorprothixene and its metabolites in breast milk

Summary Chlorprothixene (CPX) and CPX sulphoxide were demonstrated in breast milk from two psychotic mothers taking 200 mg CPX daily. The milk concentrations of CPX were 120 to 260% greater than in plasma. The estimated amounts of drug administered in breast milk to one of the infants were 15 and 26 µg/day for CPX and CPX sulphoxide, respectively. Accordingly, the infant dose of the parent compound would be only 0.1% of the maternal dose/kg body weight. It is not likely that CPX or its metabolite would exert any immediate pharmacological effects in the nursing infant. However, the long term effect of low doses of neuroleptic drugs in the developing infants is not yet known.     

76例癫痫患者苯妥英血药浓度监测

目的:分析苯妥英治疗癫痫血药浓度与剂量、疗效的关系。方法:以荧光偏振免疫法(FPIA)对171例次癫痫患者进行苯妥英血药浓度监测。结果:有效控制癫痫发作的浓度为(12.9±6.5)μg·ml-1,其中10～20μg·ml-1范围内的占54.72%。剂量0.3g·d-1时,平均血药浓度为(13.6±7.0)μg·ml-1,约60%的病例癫痫得到有效控制,2.4%发生中毒。结论:苯妥英血药浓度监测具有重要的临床意义     

Tolerability and steady-state pharmacokinetics of terodiline and its main metabolites in elderly patients with urinary incontinence

Summary The elderly form an important target group for the treatment of urinary urge incontinence with drugs such as terodiline (Mictrol, Terolin). In order to evaluate its steady-state pharmacokinetics and tolerability in geriatric patients terodiline 12.5 mg b.d. was given to 28 hospitalized patients with urinary incontinence (mean age 85 years) for six weeks. The patients were monitored during the study and for 6 weeks afterwards, blood samples being taken at regular intervals. In addition to these multi-diseased and polymedicated patients, a small, homogenous group of healthy volunteers (mean age 40 years) was studied as a reference group, being given terodiline 12.5 mg b.d. for 2 weeks.Terodiline was generally well tolerated by the patients and no significant change in blood pressure or heart rate were found. One patient was withdrawn due to adverse effects. The mean terminal half-life of terodiline was 131 h and the clearance after oral administration (clearance/systemic availability) was 39 ml·min^–1. The corresponding figures for the healthy volunteers were 57 h and 75 ml·min^–1.The average steady-state serum concentration was 518 µg·l^–1 in the geriatric patients and 238 µg·l^–1 in the healthy volunteers. Steady-state was reached within 3 weeks in 20 of the 28 patients and within 5 weeks in 7 patients.In the geriatric patients the steady-state serum concentration of the main metabolite p-hydroxyterodiline, during the last three weeks on terodiline was 45 µg·l^–1, 57 µg·l^–1, and 45 µg·l^–1, respectively, and a similar value was found in the healthy volunteers, 47 µg·l^–1. The serum concentration of p-hydroxy-m-methoxyterodiline was <15 µg·l^–1 both in the geriatric patients and in the healthy volunteers.Thus, terodiline 25 mg/day given to fragile elderly patients was well tolerated. It produced serum concentrations similar to those found after the standard dose of 37.5–50 mg given to younger, healthier patients.     

Steady-state levels of imipramine and its metabolites: Significance of dose-dependent kinetics

Summary Seventeen hospitalized patients (age 39–66 years), received a loading dose of 100 mg imipramine HCl and then 50 mg b.i.d. The 12-h plasma concentration at steady-state varied between 40–637 nmol/l for imipramine, 49–1148 nmol/l for desipramine and 89–1603 nmol/l for imipramine + desipramine. Guided by plasma level monitoring, a final therapeutic plasma level between 548–910 nmol/l for imipramine + desipramine was achieved (therapeutic dose range: 50–400 mg/day). Mean time to reach the therapeutic level was 19 days. The mean 2-OH-imipramine/imipramine ratio was 0.24 and mean 2-OH-desipramine/desipramine ratio was 0.56. There was a significant intrapatient correlation between the two ratios, both during 100 mg imipramine/d and at the therapeutic dose level. A low ratio was associated with high imipramine and particularly with a high desipramine level. Well defined steady state levels were established at two different dose levels in 12 patients and at three dose levels in 5 patients. With increasing dose there was a marked and disproportionate rise in the desipramine level and to some extent in the imipramine level. Saturation of imipramine and desipramine hydroxylation appeared to be responsible for the dose-dependent kinetics. Concomitant treatment with levomepromazine and perphenazine in one patient resulted in a significant rise both in imipramine and desipramine concentration, apparently due to inhibition of the hydroxylation. Eleven out of twelve endogenously depressed patients responded completely to treatment, whereas the response was poor in the non-endogenously depressed patients despite optimal drug levels.     

托吡酯对癫痫病人胰岛素及瘦素水平的影响

目的:研究托吡酯对癫痫病人的胰岛素和瘦素水平的影响。方法:选取35例未服用托吡酯(对照组)及55例服用托吡酯(托吡酯组)的癫痫病人,应用放射免疫技术检测其空腹胰岛素和瘦素水平并进行比较。结果:托吡酯组空腹胰岛素水平低于对照组(P<0．05);托吡酯组女性病人的空腹胰岛素水平低于对照组女性(P<0．05);2组内男性病人的瘦素水平均低于女性(托吡酯组P<0．05,对照组,P<0．01)。结论:托吡酯可显著降低非肥胖女性癫痫病人的空腹胰岛素水平,对瘦素水平无显著影响。     

Psychomotor impairment and anticonvulsant therapy in adult epileptic patients

Summary Using a battery of simple tests, psychomotor performance was assessed in 11 healthy subjects, 14 untreated epileptic patients and 66 epileptics on chronic anticonvulsant medication. Significant differences were found between controls and untreated patients for choice reaction time, card sorting and Simple Simon memory game. Treated patients performed less well than both untreated epileptics and controls in choice reaction time (p<0.05; p<0.001), card sorting (p<0.01; p<0.001), Simple Simon (p<0.05; p<0.001) and finger tapping (p<0.05; p<0.001). Patients with centrencephalic epilepsy were slower than those with discrete focal EEG abnormalities in reaction time and card sorting. Patients receiving treatment with carbamazepine, phenytoin or sodium valproate alone all performed similarly to each other and to those patients taking anticonvulsant polypharmacy. Monotherapy patients with potentially toxic plasma anticonvulsant concentrations did no worse than those within or below the therapeutic range. Both the disease and its treatment reduce psychomotor performance. All major anticonvulsants appear to cause a similar degree of impairment across a wide range of concentrations. The effect of chronic anticonvulsant medication on quality of life should not be neglected in the pursuit of perfect seizure control.