共查询到20条相似文献,搜索用时 15 毫秒
2.
A significant drug interaction between verapamil and digoxin, resulting in elevated serum digoxin concentrations, has been well documented in the medical literature. However, a similar interaction between digoxin and the calcium channel blockers nifedipine and diltiazem has not been conclusively established. This study investigated the influence of diltiazem hydrochloride on trough serum concentrations of concurrently administered digoxin in eight healthy volunteers. During the control phase of the study, volunteers were administered digoxin 0.25 mg/d for 13 days, and subsequently judged to be at steady state by serial determinations of digoxin serum concentrations. Twenty-four hour urine collections were done for creatinine clearance and urinary digoxin clearance determinations. Phase II of the study involved the addition of diltiazem hydrochloride 30 mg qid to the on-going, daily regimen of digoxin. After 14 days of concomitant therapy, steady-state trough digoxin concentrations were again determined, as well as creatinine clearances and urinary digoxin clearances. This investigation demonstrates that concomitant administration of diltiazem hydrochloride with digoxin results in significantly elevated steady-state trough digoxin concentrations (0.32 +/- 0.07 ng/ml increasing to 0.48 +/- 0.06 ng/ml, p less than 0.01). Urinary digoxin clearance decreased from 223.5 +/- 35.7 ml/min to 153.4 +/- 17.5 ml/min (p less than 0.05). Creatinine clearances were unaltered. A review of the current literature on this topic is included. 相似文献
3.
Evidence has accumulated about the involvement of reactive oxygen species (ROS) in epilepsy. The neuromodulator melatonin has been shown to reduce oxidative stress in various animal models due to its free radical scavenging properties. The present study investigated whether carbamazepine and valproate alter serum concentrations of melatonin. Epileptic children were randomly assigned to receive carbamazepine/ valproate monotherapy till 22 patients were recruited in the study. At the tenth day, in the evening, samples were drawn for baseline endogenous melatonin estimation. The patients were then administered exogenous melatonin, and repeat samples were drawn after 30 minutes. Serum levels of melatonin were estimated using Melatonin ELISA kits. The median levels of melatonin were 165.0 pg/ml (Range 50.0-350.0) in CBZ+MEL group and 78.0 pg/ml (Range 13.0-260.0) in the VPA+MEL group. The observed difference in melatonin levels could be attributed to the difference in antiepileptic drugs, additive increase in reactive oxygen species due to disease combined with carbamazepine, or possibly to a difference in melatonin kinetics in conditions of oxidative stress. 相似文献
4.
本文采用高效液相色谱法测定卡马西平与地尔硫的血药浓度,在九只家兔中按正交拉丁方设计比较单用卡马西平、地尔硫和合用两药时体内的双向药物浓度变化和药物动力学参数。结果表明,两药合用时他们的半衰期或消除速度常数比单用有显著变化,建议避免两药合用。在实验中发现卡马西平有双峰现象,估计与肠─肝循环有关。 相似文献
6.
The combination of carbamazepine and an antidepressant (doxepin, amitriptyline, mianserin) was given to 22 psychiatric inpatients with 29 measurements of their serum antidepressant concentrations. For comparison, sex-, age-, and dose-matched inpatients, treated with the antidepressant but not with carbamazepine, were selected as controls (N = 29). All the patients were treated with their routine daily dose for at least 7 days before the gas-chromatographic measurement of serum predose concentrations of the antidepressants. In patients with carbamazepine, serum doxepin and doxepin + nordoxepin concentrations (N = 17) were decreased significantly (p less than 0.05), on average to 46% and 45%, respectively, as compared to that in subjects without carbamazepine. Also in carbamazepine + amitriptyline patients, serum nortriptyline and amitriptyline + nortriptyline concentrations (N = 8) were significantly lower than in those not receiving carbamazepine (p less than 0.05). The mean serum antidepressant levels were decreased to 42% and 40%, respectively. The serum mianserin concentration of carbamazepine patients (N = 4) was reduced to 30% of that in patients not treated with carbamazepine (p less than 0.01). The percentage fractions of demethylated metabolites (nordoxepin, nortriptyline) from the total antidepressant levels were not influenced by carbamazepine. In patients treated with carbamazepine, serum total antidepressant concentrations remained more often below the suggested therapeutic ranges than in those patients without carbamazepine. The results suggest that serum antidepressant concentrations are reduced by concurrent carbamazepine therapy, and that the concentrations should be carefully monitored when carbamazepine is added to the antidepressant regimen. 相似文献
7.
The effect of serum separator tubes (SSTs) on free and total serum phenytoin and carbamazepine concentrations was determined by comparing standard no-additive tubes with SSTs (Becton Dickinson SST and Terumo Autosep). The influence of time prior to centrifugation, sample volume, and initial drug concentration on the effects were also studied. Results were analyzed using repeated measures two-way analysis of variance with tube type and either time, sample volume, or concentration as main effects. The most significant reductions noted were with Becton Dickinson SSTs in free and total serum phenytoin and total carbamazepine concentrations, where all reductions were less than 10%. The only factor to significantly influence extent of reduction was the effect of time on total serum phenytoin concentration in Becton Dickinson SSTs. Terumo Autosep tubes caused no major reductions in free or total phenytoin or carbamazepine serum concentrations. Autosep tubes should provide accurate measurements of total and free serum phenytoin and carbamazepine concentrations. With Becton Dickinson SSTs, the reductions noted in free and total phenytoin and total carbamazepine concentrations were not large enough to preclude their clinical use. Becton Dickinson SSTs should not be used for determining free or total phenytoin or total carbamazepine concentrations for purposes of research. 相似文献
8.
The hepatic cytochrome P450 enzyme system is involved in the metabolism of numerous drugs. Specific enzymes are associated with the metabolism of specific drugs. The potential for drug interactions arises when one drug inhibits or induces the enzyme(s) responsible for metabolism of another drug given concurrently. Most psychotropics are metabolized by these enzymes. Clinically significant drug interactions are reported between the selective serotonin reuptake inhibitors and other psychotropics. Specifically, interactions between fluoxetine and phenytoin are reported with substantial elevations of phenytoin concentrations. Phenytoin is metabolized by the CYP2C subfamily, and fluoxetine is known to inhibit this subfamily. Similarly, sertraline also inhibits the CYP2C subfamily, but no case reports to date have been identified. To minimize and prevent these interactions, one must be aware of the P450 enzymes involved in drug metabolism. The significance of these interactions seems to rely both on the concentration of the drug at the enzyme and its potency for inhibiting the enzyme. Frequent monitoring of serum concentrations of drugs with a narrow therapeutic range would be appropriate when a potential inhibitor is added. This article describes an apparently similar interaction between sertraline and phenytoin in two elderly patients, which resulted in elevated phenytoin concentrations without symptoms of toxicity. 相似文献
9.
目的:考察丙戊酸、卡马西平血清样品保存条件对血清药物浓度的影响.方法:取癫痫患者血清样品,在取血当天、冰箱冷藏(5 ℃±l℃)保存7 d、常温(23℃±2℃)保存7 d与14 d后,用荧光偏振免疫法测定血清丙戊酸、卡马西平浓度并进行比较,考察其稳定性.结果:室温保存7 d、14 d或冷藏保存7 d的血样测定结果与取血当天测定结果比较无统计学差异.结论:丙戊酸、卡马西平血清样品在室温下可稳定保存14d. 相似文献
10.
1例93岁女性患者因反复呕吐、进食困难入院,肾功能检查示血清肌酐90μmol/L,尿素10mmol/L。给予复方氨基酸注射液500ml和丙氨酰谷氨酰胺注射液100ml静脉滴注,1次/d。入院第5天患者血清肌酐122μmol/L,尿素51mmol/L,未予特殊处理。第12天血清肌酐120μmol/L,尿素62mmol/L,K+6.0mmol/L,Na+157mmol/L,C1-134mmol/L。患者出现神志模糊。停用复方氨基酸和丙氨酰谷氨酰胺注射液,同时控制钾、钠和补液量。4d后因患者病情再次给予肠外营养液,但仪静脉滴注复方氨基酸注射液500ml/d,共1周。复查血清肌酐126μmol/L,尿素29.7mmol/L。此后患者尿素水平未再升高。 相似文献
11.
目的:探讨抗癫痫类药物血药浓度监测结果对临床个体化给药的指导意义。方法:运用荧光偏振免疫法测定血药浓度,对我院1999年~2002年6月主要抗癫痫药丙戊酸钠、卡马西平血药浓度监测结果进行分析、评价。结杲:抗癫痢类药物有效剂量个体差异大,联合用药时抗癫痫类药物体内的相互作用复杂,血药浓度监测对临床调整用药剂量有指导意义。结论:血药浓席监测是保证临床治疗效果及用药安全的重要措施之一。 相似文献
12.
The influence of carbamazepine on the glucuronidation of the antipsychotic olanzapine was studied in a group of psychiatric patients. Steady-state serum concentrations of free and glucuronidated olanzapine were measured in 31 psychiatric patients in monotherapy (dose range, 2.5-30 mg/d; median, 15 mg/d) and in 16 patients being comedicated with carbamazepine (dose range, 5-50 mg/d; median, 20 mg/d). The concentrations were determined by HPLC with and without acid hydrolysis of glucuronidated olanzapine. For the monotherapy group, the concentrations of free and glucuronidated olanzapine ranged from 0 nmol/L to 292 nmol/L (median, 94 nmol/L) and from 0 nmol/L to 180 nmol/L (median, 27 nmol/L), respectively. The serum concentrations of the carbamazepine-treated group ranged from 21 nmol/L to 310 nmol/L (median, 81 nmol/L) and from 0 to 376 nmol/L (median, 57 nmol/L) for free and glucuronidated olanzapine, respectively. Two patients with outlying values were excluded from further analysis. The median concentration-to-daily dose ratios (C/D) of free and glucuronidated olanzapine in the monotherapy group were 5.8 nmol/L/mg and 2.2 nmol/L/mg, respectively (n =30). The corresponding values for the group comedicated with carbamazepine were 3.6 and 3.1 nmol/L/mg (n =15). Thus, the median C/D of free olanzapine in the carbamazepine group was 38% lower than that of the monotherapy group (P <0.01), confirming that carbamazepine accelerates the metabolism of olanzapine. Further, for the carbamazepine group the median glucuronidated olanzapine fraction constituted 79% of the free fraction compared with 43% for the monotherapy group (P <0.01), which suggests that an increased rate of olanzapine glucuronidation contributes to the increased rate of metabolism of olanzapine induced by carbamazepine. 相似文献
13.
本文选用单纯法,经少量目标性试验,获得了分离测定极性相差巨大的卡马西平和地尔硫卓高效液相色谱流动相条件,为开辟流动相条件选择的新途径以及临床研究药物相互作用,提供了方便。 相似文献
14.
1 Serum and CSF samples of patients receiving chronic carbamazepine treatment were analysed. 2 Daily fluctuations in serum levels of carbamazepine and carbamazepine-10,11-epoxide did not appear to be related to the dosage schedule, but some patients tended to have lower fluctuations when the carbamazepine was given more frequently. 3 The epoxide/carbamazepine serum ratios varied greatly from patient to patient, and also fluctuated during the day for the same patient. 4 Carbamazepine and carbamazepine-10,11-epoxide were present in CSF in concentrations ranging from 19 to 34% and 26 to 71% of the serum concentrations, respectively. 5 There was a significant relationship between the free fraction of both drugs evaluated in vivo and the CSF/serum ratios. 6 The need for a careful evaluation of the possible clinical effect of the epoxide is stressed. 相似文献
16.
目的分析AxSYM与RP-HPLC两种方法测定卡马西平血药浓度结果相关性。方法利用AxSYM和RP—HPLC两种方法同时测定卡马西平血药浓度,以AxSYM测定值为X,RP—HPLC测定值为Y进行线性回归,评价其相关性。结果92组数据经线性回归得回归方程:Y=0.013731+0.969354x(n=92,r=0.992451)。结论AxSYM测定卡马西平血药浓度结果与RP—HPLC测定结果具有较好相关性,适用于卡马西平血药浓度的常规监测。 相似文献
17.
During a carbamazepine (CBZ) relative bioavailability study involving tablets and a syrup preparation, salivary drug concentrations appeared disproportionately high relative to simultaneous plasma drug concentrations in the first 2-3 h after oral drug intake. This raised the suspicion of contamination of saliva by retention of drug in the mouth. In a separate study CBZ was retained in the mouth in tablet form (whole or crushed) or in syrup, for only 5 s before being spat out, and the mouth was carefully rinsed. Despite this, measurable salivary concentrations, sufficient to cause substantial error if extrapolated to simultaneous plasma drug concentrations, were present for at least 2 h after drug administration. CBZ in these studies disappeared from saliva with an apparent mean half-life of 21.0 +/- 4.8 min. This experience suggests that, in therapeutic drug monitoring, salivary CBZ concentrations for at least 2 h after dosage may lead to invalid conclusions about simultaneous plasma CBZ concentrations. 相似文献
18.
An open cross-over randomized clinical trial was performed in nine healthy humans to determine steady-state pharmacokinetics and bioavailability of three oral diltiazem preparations, tablets containing 60 and 90 mg of diltiazem hydrochloride, administered in total daily doses of 180 mg. Serum drug levels were determined by gas chromatography with electron capture detection following a simple extraction procedure. Blood samples were collected before and at several post-dosing intervals after administration of the last dose in steady state, and pharmacokinetic parameters were calculated. The steady-state diltiazem concentrations in sera were determined 48 h after the first dose, and were (mean ±SD): 46.4 ± 28.1, 60.8 ± 36.3 and 36.8 ± 22.6 μg l −1 for Pliva 60, Pliva 90, and Aldizem 90 diltiazem preparations, respectively. The corresponding elimination half-lives were 5.6 ± 2.0, 5.2 ± 1.8 and 6.9 ± 3.2 h; peak concentrations were 88.4 ± 29.5, 153.5 ± 86.5 and 139.2 ± 72.5 μg l −1, and areas under the concentration curves (AUC 12 h) were 477.4 ± 172.5, 989.2 ± 536.3 and 817.9 ± 494.5 μg h l −1 respectively. 相似文献
19.
High-dose inhaled tobramycin has been increasingly used for treatment and suppression of Pseudomonas aeruginosa pulmonary infections, especially in patients with cystic fibrosis. The advantage of inhalation over other routes of administration is minimal systemic absorption, which reduces the potential for adverse effects. However, cases of adults who had elevated serum concentrations and experienced systemic adverse effects due to excessive systemic absorption after inhaled tobramycin have been reported. We describe a prematurely born infant with numerous congenital and acquired disorders who required assisted mechanical ventilation and a 60-day stay in the neonatal intensive care unit (NICU). Tracheostomy and mechanical ventilatory support were required throughout the infant's hospital stay. The patient developed several pulmonary infections caused by various bacteria. He was treated with multiple antibiotics, including two different dose preparations of inhaled tobramycin 80 mg and 300 mg, administered through the tracheostomy and the ventilator. The infant was given a total of five preparations of tobramycin 80 mg/dose and three of 300 mg/dose, for a total cumulative dose of 1,300 mg over a 6-day period. His tobramycin concentrations increased, prompting discontinuation of the inhaled tobramycin. The infant died on day 60. To our knowledge, this is the first report of elevated tobramycin concentrations after inhalation in an infant. Although studies have found that tobramycin is safe and effective, certain patient populations are more at risk for toxicity. Tobramycin concentrations should be closely monitored in patients with significant underlying renal disorders, especially those in age-group extremes. 相似文献
20.
Plasma concentrations of carbamazepine were monitored in 9 pregnant epileptic patients treated with the drug alone at constant doses during pregnancy and for at least 3 months after delivery. In addition, plasma concentrations of the metabolite, carbamazepine 10,11-epoxide were measured in 6 of the 9 patients. Plasma carbamazepine concentrations were fairly stable during pregnancy, and carbamazepine relative plasma clearances were significantly higher in weeks 4 to 24 than in weeks 25 to 32. After the end of the second trimester, there were no variations in plasma carbamazepine 10,11-epoxide concentrations and carbamazepine 10,11-epoxide:carbamazepine ratios. Both parameters were significantly higher in weeks 4 to 24 than in weeks 25 to 32 of pregnancy. 相似文献
|