ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Nearly 2 decades have passed since initial studies demonstrated a relationship between plasma (or serum) levels of the tricyclic antidepressant drugs and clinical response. Since then, therapeutic monitoring of antidepressant drugs has become routine in many laboratories and the use of these measures is becoming a routine part of psychiatric practice. New uses for antidepressant measurements have evolved and guidelines for proper use of these measures need to be updated to take advantage of more recent findings. Continuing studies in psychiatry have also prompted technical advances in methodology that has undergone predictable evolution to robust techniques for analysis of most antidepressants. However, the diversity of methods for therapeutic drug monitoring, issues of cross-reactivity and assay interferences, and confusion over sample collection techniques still contribute to difficulties in obtaining and using serum concentration data. Differences between techniques specifically designed for therapeutic monitoring of antidepressant drugs and those designed for toxicology or emergency drug screening are not clear and lead to misunderstandings between laboratory personnel and psychiatrists. This article updates and discusses current guidelines that form the basis for using serum level measurements of antidepressant drugs and reviews salient pharmacologic, clinical, and analytical issues that must be taken into account if therapeutic drug monitoring data are to be used for optimal clinical benefit.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Steady-state plasma levels of nortriptyline and E- and Z-10-OH-nortriptyline were determined in 55 depressed patients during long-term treatment. Dose-corrected steady-state levels varied by a factor of 20 for nortriptyline, a factor of 7 for E-10-OH-nortriptyline (sum of enantiomers), and a factor of 12 for Z-10-OH-nortriptyline (sum of enantiomers). The E-10-OH-nortriptyline levels were higher than the corresponding nortriptyline levels in about 50% of the patients and the nortriptyline/E-10-OH-nortriptyline ratio ranged from 0.27 to 4.8. In contrast to E-10-OH-nortriptyline, the steadystate levels of Z-10-OH-nortriptyline correlated significantly with the nortriptyline levels (rs= 0.68,n= 55,p< 0.001) and the nortriptyline/ Z-10-OH-nortriptyline ratio ranged from 1.7 to 10. Patients on concurrent treatment with perphenazine or benzodiazepines had higher nortriptyline and nortriptyline/E-10-OH-nortriptyline ratios than patients taking lithium or no other psychotropic drugs. A sparteine test was carried out in 22 patients and the sparteine metabolic ratio correlated significantly with the dose-corrected steady-state levels of nortriptyline (rs= 0.62,p< 0.01) and E-10-OH-nortriptyline (rs= −0.52,p< 0.02) and particularly well with the ratio nortriptyline/E-10-OH-nortriptyline (rs= 0.83). The genetic variability in the sparteine/debrisoquine P-450 isozyme appeared to be clearly more important for the interindividual variation in 10-hydroxylation of nortriptyline than the possible interactions with concurrent medication.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of an enteral nutrient formula (Osmolite) on the absorption of a single oral dose of sustained-release theophylline (Slo-bid) was studied in healthy men. In a randomized, crossover design, subjects received the enteral nutrient diet (2,400 ml/day) or food diet (F) of similar caloric, fat, carbohydrate, protein, and sodium content for 7 days. On day 6 of each diet, volunteers received a single oral dose (600 mg) of sustained-release theophylline (SRT) after fasting or with hourly oral boluses (100 ml) of enteral nutrient formula (ENF). Serial blood samples were collected for 48 h and serum concentrations were analyzed by enzyme multiplied immunoassay. Slight differences (p < 0.01; pairedttest) inCmax(7.1 \pm 1.2 versus 8.2 \pm 1.3 mg/L) andTmax, (10.7 \pm 2.4 vs. 7.1 \pm 1.1 h) were observed between the ENF and F diets, respectively. However, areas under the curve values were similar (215 \pm 72 versus 211 \pm 70 mg h/L). This study suggests that ENF does not affect the extent of absorption of SRT when administered as a single oral dose.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of viloxazine on the pharmacokinetics of theophylline was studied in eight healthy volunteers. Theophylline 200 mg/day (théophylline Bruneau 100 mg tablets) was administered on day 1; after a 3-day washout period, viloxazine 300 mg/day (Vivalan 100 mg tablets) was administered orally from days 5 to 7. On day 8, theophylline 200 mg and viloxazine 100 mg were concomitantly administered. The pharmacokinetic parameters of theophylline alone and after coadministration of viloxazine were determined. Viloxazine significantly increased the plasma concentrations (p < 0.01) and the areaunder-the-curve values (p < 0.01) of theophylline and decreased its body clearance (p < 0.05). Our results suggest that the dosage of theophylline should be decreased and its plasma concentrations monitored when viloxazine is prescribed.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Twenty-four nonsmoking male volunteers took 50 mg atenolol or 10 mg betaxolol orally once a day for 9 days in a two-period, four-sequence, randomized, crossover study. Plasma concentrations reached steady state after day 5. Percent fluctuation in plasma concentration defined as (Cmax–Cmin)/Cavg(% fluctuation 1) was 97% on day 9 for betaxolol and 343% for atenolol; thus atenolol fluctuation was more than threefold that of betaxolol. A 10-fold difference in plasma level fluctuation was observed when fluctuation was defined as (Cmax–Cmin)/Cmin(% fluctuation 2). The intersubject variances for % fluctuation 1 and % fluctuation 2 were 4.1 and 85.5 times greater for atenolol than for betaxolol; these differences were marginally statistically significant for % fluctuation 1 and significant for % fluctuation 2. The intra-subject variabilities for area under the curve and plasma level fluctuations were statistically greater for atenolol than for betaxolol. Atenolol intrasubject variances were 25 and 271 times greater than for betaxolol for % fluctuation 1 and % fluctuation 2, respectively. Thus, betaxolol exhibited less fluctuation in plasma levels with substantially less intersubject and intrasubject variability. These factors would be expected to provide a more consistent therapeutic response and more dependable dosage adjustment.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The relationship between free carbamazepine fraction (F-CBZ-F) and valproic acid (VPA) was studied in 50 outpatients coming for regular visits to our clinic throughout the day, and was compared with 50 patients without VPA comedication under similar conditions. F-CBZ-F was found to be significantly (t= 3.5,df= 98, p < 0.001) higher for VPA comedicated patients (0.291 \pm 0.024) when compared with patients without VPA (0.247 \pm 0.016). Linear regression analysis for total plasma VPA concentration versus F-CBZ-F gave the equation: F-CBZ-F = 0.247 + 0.00062 (VPA); n = 50,r= 0.697, p < 0.001, indicating unreliable prediction of F-CBZ-F from VPA concentration. Substituting the parameter F-CBZ-F by its equivalent (F-CBZ/CBZ) yielded the equation F-CBZ = [0.247 + 0.00062 (VPA)] CBZ. The predictive power of this equation was evaluated by the comparison of obtained and predicted F-CBZ concentrations. An excellent agreement (n = 50,r= 0.981, p < 0.001) was obtained. Although the empirically derived constants of the equation are not unique and may vary depending on the conditions of different methodologies, the fundamental relationship has been established and can be used to reliably predict F-CBZ concentration from plasma VPA and CBZ concentration.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of a dose change on the plasma concentration of carbamazepine (CBZ) was studied in 13 epileptic patients, all with a CBZ dose of at least 800 mg/day. A disproportionately small rise in the plasma concentration of CBZ was found in 10 of the patients. The ratio between the final metabolite 10,11-dihydro-10,11-trans-dihydroxy-CBZ and CBZ in plasma was higher after dose increase in the 10 patients with a small rise in CBZ levels, indicating a dose-dependent autoinduction of CBZ metabolism. The ratio between the active intermediary metabolite, CBZ-epoxide, and CBZ was unaltered by the dose change in all patients. This indicates that CBZ plasma level determinations can be used for prediction of the total effect of CBZ treatment during high as well as low dosage.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

An increase in the time required to achieve the peak plasma concentration is observed following the oral administration of increasing doses of phenytoin. Zero-order absorption is the usual explanation for this observation. The presence of Michaelis-Menten elimination also increases the peak time when absorption is first order. The contribution of each of these mechanisms in vivo is unknown.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In a complete crossover study, balanced for sex and treatment order, we have investigated the pharmacokinetics of diltiazen in 10 healthy middle-aged volunteers. The treatments were 60 mg t.i.d. and 120 mg t.i.d. during 14 days' treatment, with the last dose pulsed with 1.85 MBq [14C]diltiazem. The absorption was rapid and did not differ between treatments. The disposition could be appropriately described using a two-compartment model with terminal half-lives of 6.57 \pm 1.41 h (mean \pm SD) after 60 mg t.i.d. and 5.44 \pm 0.66 h after 120 mg t.i.d. The half-life of the metaboliteN-demethyldiltiazem (MA) was similar to that of diltiazem, whereas the halflives of deacetyldiltiazem (M1) andN-demethyldeacetyldiltiazem (M2) were longer. The plasma concentrations and areas under the curve found after doubling of the dose were not significantly different from dose-adjusted directly proportional estimations. However, the mean concentration of MAin percent of diltiazem concentration was significantly higher at the lower-dose regimen 41 \pm 11% versus 36 \pm 8%, whereas the corresponding values for M1were 11 \pm 3% versus 11 \pm 4% and for M212 \pm 4% versus 12 \pm 6%, respectively. The median cumulative excretions of radioactivity during 120 h were 90 and 93%, respectively. The drug was mainly excreted in urine (73 versus 73%, median), the remaining amounts were eliminated in feces.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID