摘要:

In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10,11-epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased conceatration ratios of trans-10,11-dihydroxy-10,11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = VPA-2004e7.942+0.014-VPAor = VPA-2.004e3.299+0.014-VPA, respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Few Studies have been published on the pharmacologic response to treatment of patients whose seizures begin after 40 years of age. The purpose of this study was to assess the impact of chronic pharmacotherapy on the seizure control of such patients. We retrospectively studied the seizure frequency recorded during a 12-month period in a group of 94 outpatients whose seizure disorders began after 40 years of age (median age of seizure onset 56.5 years) and who had been treated with anticonvulsant medication for a median period of 6 years (range 18 months to 12 years). We assessed the relationship between the patients' seizure frequency during the last 12 months of treatment using (a) the present and previously prescribed pharmacologic regimens, (b) anticonvulsant blood levels of present regimen, (c) etiology and duration of seizure disorder, (d) age at onset of seizures, and (e) presence of electrographic (EEG) and neuroradiologic abnormalities. We only identified side effects occuring at blood levels within or below the drug's therapeutic range. Seventyeight patients (83%) were seizure free during the last 12 months of treatment, 11 (11%) had rare seizures, and five (6%) had more than four seizures per year. Seizure frequency was not affected by duration and etiology of seizure disorder, age at onset of seizures, seizure type, neuroradiologic or electroencephalographic abnormalities, and present or previously prescribed pharmacologic regimens. Persistent side effects were reported in seven of 76 (9%) monotherapy regimens and in two of 12 (17%) polytherapy regimens. Our data suggest that seizures beginning after the age of 40 have a favorable prognosis after chronic pharmacotherapy.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Felbamate is a new antiepileptic drug (AED) with a good safety profile. Anorexia has been reported in patients taking felbamate, but the incidence and severity of this side effect have not been adequately investigated. We studied 65 patients with intractable seizures who received adjunctive felbamate therapy as part of clinical research trials or in a compassionate-use program. Mean treatment time on felbamate was 23 weeks (±SD 16; range, 6–116 weeks). Forty-nine patients (75%) lost weight during the trials. For subjects older than 15 years, there was a mean weight loss of 3.17 kg or 4.11% of body weight (T = 191.5,z= 4.18,p< 0.001). For subjects 15 years or younger, there was a mean weight loss of 0.20 kg or a loss of 1.77% of body weight (T= 52.5, NS). Twenty-two patients (34%) lost >4 kg, and seven patients (11%) lost <8 kg. Adjunctive treatment of adults with severe epilepsy with felbamate may be associated with clinically significant weight loss.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Cycloserine acts as a potent and selective modulator of the N-methyl-D-aspartate (NMDA) receptor-associated glycine recognition site, which may be a possible mechanism for this compound's positive effects on memory formation and retrieval processes in animals. Studies in normal human volunteers have shown that cycloserine can have significant positive effects on cognitive processing in the elderly and can ameliorate memory deficits induced by subcutaneously administered scopolamine. Based on this profile, a doubleblind, placebo controlled, parallel group (three drug dosages) study was conducted as part of a larger study to assess the efficacy and safety, as well as the cognitive and central nervous system (CNS) impact, of 6 months of cycloserine treatment in patients (N = 40) with probable dementia of the Alzheimer type (DAT). The Cognitive Drug Research Computerized Assessment System (CDR System) served as the priamry outcome measure of efficacy. CNS activity was assessed using quantified electroencephalography (QEEG). Safety measures included adverse effects documentation and analysis of blood chemistry/hematology. Cycloserine proved to be a safe agent in this population at the doses given but failed to show any statistically significant effects in the areas of cognition and global clinical ratings and did not indicate significant CNS activity on QEEG. These findings suggest that cycloserine has no measurable therapeutic effect on Alzheimer's disease at the doses given.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Remoxipride is a novel substituted benzamide that more effectively blocks mesolimbic than striatal D2 dopamine receptors. We used remoxipride in the management of nine patients with Parkinson's disease (PD) who were experiencing visual hallucinations due to dopaminergic therapy. Remoxipride was begun in a dose of 25 mg three times daily and gradually increased to 75–225 mg/d (mean 161 mg). The psychiatric status improved in eight patients. Little or no change in the severity of parkinsonism was noted in five, a mild increase in two, and a moderate increase in two. Because one patient with moderately severe levodopa-induced dyskinesins experienced a reduction in the abnormal movements without a substantial increase in parkinsonism, we began a trial of remoxipride for disabling peak-dose dyskinesias. The trial was abandoned after every one of the first four patients entered experienced an immediate, severe, and prolonged increase in off periods with single 10− to 25-mg doses. This striking differential response to an atypical neuroleptic with weak striatol D2 antagonist properties indicates that different states of postsynaptic dopamine receptor sensitivity or synaptic dopamine levels may be associated with various disease- and treatment-related problems found in late-stage PD.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We studied the effect of entacapone, a catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of a controlled-release (CR) levodopa-carbidopa preparation (Sinemet CR) in an open, randomized trial in 12 healthy male volunteers. The inhibition of soluble COMT (S-COMT) in red blood cells (RBCs) was also measured. Singie graded doses of entacapone (100–800 mg) were administered concomitant with a single oral dose of CR levodopa, or CR levodopa was given without entacapone (control treatment), at least 1 week apart. Plasma concentrations of levodopa, 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), carbidopa, and entacapone were determined for pharmacokinetic calculations. Entacapone decreased dose-dependently the activity of S-COMPT in RBCs with a maximal inhibition of 66% after the highest dose (800 mg). Entacapone increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was highest (33%) after the 400-mg dose. Entacapone did not influence time to maximal concentration (Tmax) of levodopa. Entacapone was absorbed faster than levothat of DOPAC increased dose-dependently after entacapone, maximally by 69, 38, and 74%, respectively. Higher doses of entacapone (400 mg and 800 mg) decreased the AUC, but notTmaxof carbidopa. Over the dose range studied, entacapone was well tolerated. Entacapone is an effective COMT inhibitor. It improves the pharmacokinetic profile of levodopa when used in combination with a CR levodopa preparation, as it does with a standard levodopa preparation. The results justify further clinical studies with entacapone in combination with CR preparations of levodopa.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We measured homovanillic acid (HVA), 5-hydroxy indole acetic acid (5-HIAA), and tryptophan (TP) in cerebrospinal fluid (CSF) of 20 neuroleptic-free patients with Huntigton's disease (HD), and compared mean values with those from four control groups inclnding 15 normal individuals, 38 patients with dystonia, 23 untreated patients with Parkinson's disease, and 61 patients with other/neurological diseases (ONDs). The mean levels of HVA in the CSF of patients with HD were reduced compared with those from normal controls (p< 0.001), dystonic patients (p < 0.005), individuals with ONDs (p < 0.0001), and even from untreated parkinsonian patients (p < 0.05), 5-HIAA and TP levels in the CSF of patients with HD were not significantly different from those in the CSF of control patients. Our data suggest a reduced dopamine neurotransmission in HD and may account for the bradykinesia observed in our patients.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The effects of dopamine receptor antagonists on phencyclidine (PCP)-induced behaviors were examined in rats. Acute administration with PCP (7.5 mg/kg i.p.) produced various behavioral changes, such as increases of spontaneous activity, head-weaving, sniffing, rearing, back-pedaling, and ataxia. To determine which dopamine receptor subtypes were involved in mediating the PCP-induced behaviors. SCH 23390 (0.05 and 0.5 mg/kg), sulpriride (20 and 100 mg/kg), or haloperidol (0.05 and 0.5 mg/kg) were pretreated 30 min before PCP treatment (7.5 mg/kg). A higher dose of SCH 23390 significantly reduced the increase of spontaneous activity induced by PCP. Both doses of sulpiride did not affect the PCP-induced behaviors. A higher dose of haloperidol decreased the PCP-induced spontaneous activity, wherease a lower dose of haloperidol enhanced the activity. Ketanserin (0.5 and 5 mg/kg) did not alter any PCP-induced behaviors. These results suggest that the D1, but not D2, dopamine receptor subtype may be involved in the PCP-induced behavioral abnormality.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Valproic acid has been proven to be efficient in the treatment of bipolar affective disorders as an adjunctive agent to lithium and carbamazepine. Recently, its efficacy in rapid cycling states has attracted interest. We present the case of a male patient with bipolar affective disorder who developed an extreme state of ultrapid cycling (48-h cycles). Only the addition of valproic acid therapy to prior lithium treatment succeeded in curtailing the ultra-rapid cycling. Several issues regarding ultra-rapid cycling and valproate's efficacy in bipolar disorder are discussed.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Cisapride, a substiuted piperidinyl benzamide that is chemically related to metoclopramide, is a prokinetic agent that facilitates motility of the gastronitestinal tract (1). The mechanism by which cisapride exerts its actions is not clear. It enhances acetylcholine release in the myenteric plexus of the gut, and evidence exists that it has an agonistic action on a serotonin receptor, probably the 5-HT4 receptor (2). The drug is well tolerated, and no central nervous system side effects have been reported. We describe two patients with parkinsonism who experienced aggravation of tremor while on therapy with cisapride.

ISSN:0362-5664    

出版商:OVID    

年代:1995

数据来源: OVID