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1. |
Dextromethorphan and Mephenytoin Phenotyping of Patients Treated with Thioridazine or Amitriptyline |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 1-8
Pierre Baumann,
Johann Meyer,
Marlyse Amey,
Dominique Baettig,
Christian Bryois,
Michèle Jonzier-Perey,
Liliane Koeb,
Christian Monney,
Brigitte Woggon,
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摘要:
The metabolism of most tricyclic antidepressants and some phenothiazine neuroleptics is under the genetic control of hepatic cytochrome P-450IID6, which also regulates the metabolism of dextromethorphan. This study investigated the effect of treatment with amitriptyline or thioridazine on testing for genetically regulated efficiency of the metabolism of dextromethorphan and mephenytoin. One group of 33 patients was treated with 150 mg amitriptyline a day (the AMI group); 25 other patients received a daily dose of thioridazine, either 200 mg (200-THD group; n = 7) or 400 mg (400-THD group; n = 18). Before and after 10 days of this treatment, all patients were tested with 25 mg dextromethorphan and 100 mg mephenytoin to determine their pharmacogenetic status with respect to their hepatic drug oxidizing systems (cytochrome P-450IID6 and P-450 MP). Two patients were poor metabolizers (PMs) of dextromethorphan and three of mephenytoin. Treatment with either psychotropic drug was without significant effect on the metabolism of mephenytoin, but both amitriptyline and thioridazine increased significantly the metabolic ratio of dextromethorphan/dextrorphan. Thioridazine had the effect of changing the pharmacogenetic status of 15 efficient metabolizers of dextromethorphan to poor metabolizers; amitriptyline did not have such an effect. There was no significant correlation between day-11 plasma levels of thioridazine, mesoridazine, or sulforidazine and the metabolism of dextromethorphan, but there was a correlation between the metabolism of dextromethorphan and plasma levels of amitriptyline and nortriptyline. Amitriptyline (p< 0.05), but not thioridazine, decreases the ratio of conjugated/total dextrorphan in urine. Therefore, the dextromethorphan pharmacogenetic test can be used for clinical purposes, but to avoid artefacts it should be done after a washout period, especially after treatment with thioridazine; testing with mephenytoin is less likely to be influenced by thioridazine or amitriptyline.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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2. |
Unbound Plasma Phenytoin Concentrations Measured Using Enzyme Immunoassay Technique on the Cobas MIRA Analyser—In Vivo Effect of Valproic Acid |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 9-13
Benedetta Sallustio,
Raymond Morris,
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摘要:
This communication describes a modification of the total plasma phenytoin enzyme immunoassay technique (EMIT) run on the Cobas MIRA analyser that allows quantitation of unbound phenytoin concentrations in human plasma for routine therapeutic drug monitoring (TDM) purposes. An application of this method is also presented to consider the previously described protein binding drug interaction with concomitantly administered valproic acid in patients with epilepsy. The coefficients of variation for the unbound phenytoin assay ranged from 7.5 to 9.6% and the assay had a reproducibility and accuracy similar to the total phenytoin assay, acceptable for routine TDM. Phenytoin protein binding was linear over a range of total plasma concentrations of 3–65 mg/L. Patients also receiving valproic acid (nine patients, 105 specimens) had a significantly (p< 0.0001) greater mean ± SD unbound phenytoin fraction (13.3 ± 3.1%) compared to nine patients (110 specimens) not receiving valproic acid (8.3 ± 1.6%). There was also a significant correlation (p< 0.001) between plasma valproic acid concentration and unbound phenytoin fraction, which resulted in greater intrasubject variability in phenytoin protein binding.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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3. |
Effectiveness and Side Effects of Two Different Doses of Caffeine in Preventing Apnea in Premature Infants |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 14-19
C. Romagnoli,
M. De Carolis,
U. Muzii,
E. Zecca,
G. Tortorolo,
M. Chiarotti,
N. De Giovanni,
A. Carnevale,
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摘要:
The effectiveness of caffeine citrate in preventing idiopathic apnea in premature infants was evaluated. Thirty-seven preterm infants born before the 32nd week of gestation were studied. After an intravenous loading dose of 10 mg/kg of caffeine citrate, two different oral maintenance regimens were followed: 5 mg/kg in Group I and 2.5 mg/kg in Group II. A significant decrease in the number of apneic spells occurred in both treated groups as compared with a control group. In Group II, the frequency of side effects such as tachycardia and gastrointestinal intolerance was significantly lower than in Group I. Group II theophylline plasma levels were significantly lower than those of Group I. The lower Group II theophylline levels presumably explain the reduced frequency of side effects.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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4. |
Methylprednisolone Hemisuccinate and Metabolites in Urine from Patients Receiving High‐Dose Corticosteroid Therapy |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 20-26
Graham Lawson,
Jagadish Chakraborty,
Minoo Dumasia,
E. Baylis,
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摘要:
A reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the measurement of methylprednisolone hemisuccinate (MPHS) and its metabolites methylprednisolone (MP), 20-α- (20a-HMP), and 20-β-hydroxymethylprednisolone (20b-HMP) in urine is described. The metabolites were extracted from urine samples using Extrelut columns and eluted with ethylacetate. The mobile phase for RP-HPLC comprised methanol:citrate buffer:tetrahydrofuran (30:65:5, vol/vol/vol) with UV detection at 251 nm. Fractions were collected, pooled and the metabolites present were identified by gas chromatography-mass spectrometry and normal-phase HPLC (NP-HPLC). By RP-HPLC 30 ± 7.3% (mean ± 1 SD) of the dose was detected in the 0–24 h urine sample following a 1 g MPHS infusion to patients with rheumatoid arthritis; MPHS contributed 9.9 ± 5.0%, MP 12.1 ± 2.9%, 20a-HMP 7.8 ± 2.2%, and 20b-HMP 1.0 ± 0.3%, respectively. A further 1.0 ± 0.9% of the administered dose was detected in urine collected 24–48 h postinfusion.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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5. |
Postmortem Concentrations of Phenytoin in Different Regions of the Brain and in the SerumAnalysis of Autoptic Specimens from 24 Epileptic Patients |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 27-35
B. Rambeck,
R. Schnabel,
T. May,
U. Jürgens,
R. Villagràn,
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摘要:
Postmortem concentrations of phenytoin (PHT) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex and white matter, as well as cerebellum) of 18 epileptic patients who died following chronic diseases (group A) and of six otherwise healthy epileptic patients who died suddenly and unexpectedly (group B). The free concentrations in the serum correlated considerably better (r= 0.987) than the total concentrations in the serum (r= 0.871) with the concentrations in the frontal cortex. The concentrations in the frontal cortex were about nine times that of the free serum concentrations. The data show that the PHT concentrations in the frontal, temporal and occipital cortex largely agree. The concentrations in the white matter were significantly higher (frontal region 54%, temporal region 30%, occipital region 36%) than in the cortex. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical with those in the frontal cortex. Regression analysis showed that on comparable total serum concentration the patients of group A had significantly higher free serum concentrations and significantly higher concentrations in the frontal cortex than the patients of group B. In respect of the concentration ratios cortex to serum free and in regard of the local distribution of PHT in the brain no difference, however, was found between those patients who died from chronic diseases and those who died suddenly. This means that the various diseases and organ failures which resulted in the death of the patients influenced neither the passage of PHT from the serum (free) to the brain, nor the local distribution of PHT in the brain. Our data do not support the supposition that therapy resistance or damage of the cerebellar cortex in spite of therapeutic serum concentrations are explainable by individually or locally varying concentrations in the brain.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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6. |
Steady‐State Pharmacokinetics of Rufloxacin in Elderly Patients with Lower Respiratory Tract Infections |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 36-41
Roberto Cogo,
Roberto Rimoldi,
Roberto Mattina,
Bruno Imbimbo,
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摘要:
The pharmacokinetics of rufloxacin, after repeated doses, was evaluated in 12 elderly patients with lower respiratory tract infections. Patients were given a single loading dose of 400 mg on the first day of treatment and single daily maintenance doses of 200 mg for the next 6–9 days. Serum concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at regular intervals during treatment and fitted to a one-compartment open model for repeated doses. The maximum serum concentration after the first dose was 6.46 ± 1.06 (mean ± SEM) μ/ml and was reached in 4.3 ± 0.8 h after the first administration. The elimination half-life was 28.7 ± 4.1 h. The area under the serum levels-time curve from 0 to 24 h was 103 ± 14 μg/h/ml after the first dose. On the last day of observation it increased to 155 ± 28 μg/h/ml, with a mean extent of accumulation of 2.3 ± 0.3 times. The elimination half-life was comparable to those in other studies in healthy young subjects, while plasma levels were about 80% higher. These results suggest that in elderly patients elevated drug concentrations may be reached in the serum. Although no untoward reactions related either to the drug concentration in serum or the dose have been noted with rufloxacin, this patient population should nevertheless be monitored carefully for adverse effects.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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7. |
Relative Performance of Specific and Nonspecific Fluorescence Polarization Immunoassay for Cyclosporine in Transplant Patients |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 42-47
Gary Chan,
Samuel Weinstein,
William LeFor,
Edward Spoto,
Lawrence Kahana,
Dana Shires,
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摘要:
The analytical performance of specific and nonspecific fluorescence polarization immunoassays (FPIAs, Abbott Laboratories) for cyclosporine was compared. Both specific and nonspecific FPIAs demonstrated excellent between-run coefficients of variation (5.9% vs. 3.9%) at three levels of control, and a high degree of between-center reproducibility (r2> 0.96). In addition, the correlation between cyclosporine levels measured by specific and nonspecific FPIAs was statistically significant, though imperfect, in both renal (r2= 0.70) and cardiac transplant patients (r2= 0.55). In kidney transplant patients, the nonspecific/specific ratio was significantly higher in patients with serum bilirubin concentration exceeding 3 mg/dl (5.9 ± 2.6 vs. 2.8 ± 1.1), due to impaired elimination of cyclosporine metabolites in the bile. The nonspecific/specific ratio was also significantly higher in heart transplant patients early (<1 month) posttransplant compared with patients in the late posttransplant period (3.4 ± 0.8 vs. 2.9 ± 0.8). The Abbott FPIA provides a highly precise method for measuring cyclosporine, with a turnaround time of 15–20 min. The specific monoclonal FPIA has the additional advantage of measuring primarily unchanged cyclosporine and thus has an imperfect correlation with the nonspecific polyclonal FPIA. Together with clinical data, the use of FPIAs may help to improve the efficiency of cyclosporine therapeutic drug monitoring.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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8. |
Relationship Between Serum and Saliva Theophylline Levels in Patients with Cystic Fibrosis |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 48-54
James Blanchard,
Suzanne Harvey,
Wayne Morgan,
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摘要:
Theophylline levels in stimulated and unstimulated mixed saliva were compared with total and free (unbound) serum theophylline levels in 11 outpatients with cystic fibrosis (CF) who were using theophylline regularly. Stimulated saliva from CF patients predicted both total and unbound serum theophylline concentrations to within ±1 μg/ml in 53.3 and 80.0%, respectively, of the samples examined. In addition, the total serum levels from CF patients could be used to predict unbound serum concentrations to within ± 1 μg/ml in 100% of the cases examined. Furthermore, it was observed that prediction equations derived in a previous study with asthmatics employing identical methodology would allow both unbound and total serum theophylline levels to be predicted from saliva levels in CF patients with a degree of accuracy and precision that was approximately equal to or slightly better than the results obtained using prediction equations derived in other CF patients. These results indicate that saliva levels allow predictions of the unbound serum theophylline levels with greater accuracy and precision than they predict total serum theophylline levels. In addition, total serum levels can be used to reliably predict unbound serum levels. The use of mixed stimulated saliva is recommended as a reliable noninvasive method for monitoring unbound serum theophylline levels. The therapeutic range for saliva, which corresponds to the accepted total serum concentration range of 10–20 μg/ml, is ∼5.55–11.3 μg/ml.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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9. |
Binding Parameters of Valproic Acid to Serum Protein in Healthy Adults at Steady State |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 55-60
Yasuo Kodama,
Yuichi Koike,
Hiroo Kimoto,
Fumitaka Yasunaga,
Masaharu Takeyama,
Iwao Teraoka,
Isao Fujii,
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摘要:
Two hundred milligrams of valproic acid (VPA) was administered orally to seven healthy adults at 9:00 and 21:00 h for 5 consecutive days, including the morning dose on day 6. On the sixth day, blood samples were drawn at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 3, and 6 h after the morning dose. Binding of VPA to serum protein was evaluated by ultrafiltration, and total and unbound VPA concentrations were determined by fluorescence polarization immunoassay. Binding parameters of VPA to serum protein were calculated for each subject by the Scatchard analysis. The binding parameters obtained from seven subjects showed that the mean association constant (K) was 2.72 x 104L/mol while the total number of binding sites (nPt) was 789 μmol/L. There were marked interindividual variations and the coefficient of variation was 42% forKand 28% fornPt. These results show that endogenous free fatty acids (FFAs) significantly reduce the binding affinity of VPA to serum albumin (p< 0.05). In addition, they suggest the possibility that the primary binding sites for VPA can be strongly reduced by FFAs. Therefore, we consider that interindividual differences in binding parameters may be clinically important.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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10. |
Improved High‐Performance Liquid Chromatographic Method for the Determination of Indomethacin in Plasma |
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Therapeutic Drug Monitoring,
Volume 14,
Issue 1,
1992,
Page 61-65
A. Johnson,
J. Ray,
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摘要:
Indomethacin is an inhibitor of prostaglandin synthesis and has several uses, including the ability to encourage closure of a patent ductus in premature neonates. A rapid, accurate, and sensitive high-performance liquid chromatographic (HPLC) method is described for measuring plasma concentrations of indomethacin. An acidic buffer (citrate, pH 3.0) was employed to alter the pH of the aqueous phase prior to extraction to minimise interference from endogenous compounds. Extraction of indomethacin from plasma was optimally achieved with petroleum ether (boiling fraction of 40–60°C):dichloromethane (50:50). However, separation of indomethacin from plasma proteins was attempted unsuccessfully using acetonitrile precipitation; severe band broadening occurred due to injected sample solvent problems. The absolute recoveries for indomethacin and internal standard (mefenamic acid) were over 90% (n = 3). Precision was expressed as the coefficient of variation (n = 4), which was ±8% at each of six indomethacin concentrations in the range 50–2,000 ng/ml. The limit of quantitation of indomethacin in plasma was 50 ng/ml (0.5 ml of plasma injected). We report an HPLC method for the quantitation of indomethacin in plasma that may have widespread applicability for routine drug assay laboratories.
ISSN:0163-4356
出版商:OVID
年代:1992
数据来源: OVID
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