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1. |
Methadone Maintenance Treatment: Is It Possible to Adapt the Daily Doses to the Metabolic Activity of the Patient? |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 1-3
Corinne Charlier,
Marie-Claire Dessalles,
Guy Plomteux,
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摘要:
Controversy still exists concerning the proper daily dose of methadone to be used in opiate dependency treatment. Because it is admitted that serum methadone concentration may be significantly correlated with the amount of drug available at the receptor level, it could be interesting to predict the methadone daily doses necessary to reach such a serum concentration. The authors have attempted to correlate the serum methadone level with the daily intake, considering the metabolic activity of the patients. A poor correlation was found between methadone doses and methadone serum concentrations (r2= 0.0409, p = 0.048). The test used to determine the metabolic activity of patients is the 6-OH cortisol/17-OH corticosteroids ratio in urine. This urinary 6-OH cortisol/17-OH corticosteroids ratio was tested because cortisol is metabolized through the same P450 cytochromes as methadone, namely cytochrome P450 3A4. This determination could be of interest because it could be tested before methadone administration to predict optimal doses. But when the authors tried to correlate the methadone serum concentration with the steroid ratio, they failed to find a significant correlation (r2= 0.0046, N.S.), even when they took into account the daily doses (r2= 0.0015, N.S.), most probably because of some limitations of the cortisol ratio.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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2. |
Effective Fluconazole Therapy for Liver Transplant Recipients During Continuous Hemodiafiltration |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 4-8
Satoshi Kishino,
Yuka Koshinami,
Takeru Hosoi,
Noriyuki Suda,
Yoh Takekuma,
Satoshi Gandoh,
Hiroyuki Furukawa,
Satoru Todo,
Katsumi Miyazaki,
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摘要:
Fungal infections are still one of the main causes of death and complications after solid organ and bone marrow transplants. The authors evaluated the effect of continuous hemodiafiltration (CHDF) on the pharmacokinetics of fluconazole in liver transplant recipients. Six liver transplant patients (primary biliary cirrhosis, n = 2; fulminant hepatitis, n = 2; viral hepatitis, n = 2) were enrolled in this study. In one patient not receiving CHDF, the fluconazole levels increased with increasing dosages. In contrast, in patients undergoing CHDF, the dosage of fluconazole was increased from 100 mg/d to 200 mg/d, but fluconazole did not reach the targeted levels. It appears that the targeted trough level cannot be achieved by administration of fluconazole at a dosage of 100 to 200 mg/d during CHDF. A higher dosage (600–1000 mg/d) of fluconazole may be required to achieve the therapeutic drug level in patients undergoing CHDF. In patients undergoing CHDF, fluconazole was given at a dosage of 800 mg/d and reached the targeted levels. In addition, after CHDF, the dosage of fluconazole was decreased to 100 mg/d, and fluconazole reached the near-targeted trough level. These results demonstrate that CHDF removes fluconazole from the blood at an efficiently high rate, resulting in its ineffective blood level. To guarantee safe and effective fluconazole therapy, the trough levels should be monitored routinely during CHDF.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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3. |
Prediction of Metabolic Activity From Genotype: The Gene–Dose Effect ofN-Acetyltransferase |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 9-14
Peter Meisel,
Dorit Arndt,
Eberhard Scheuch,
Klaus-Jürgen Klebingat,
Werner Siegmund,
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摘要:
Metabolic activity of the polymorphicN-acetyltransferase (NAT2) is determined by the mutation pattern of theNAT2gene. This results in interindividual differences in the metabolic capacity (the phenotype), with continuous distribution of the activities rather than qualitative distinction between rapid and slow acetylators. To determine whether the phenotype might be predicted solely from the mutation pattern ofNAT2, quantitative relationships were calculated between mutation patterns of theNAT2gene and the phenotype of NAT2 assessed either in vitro or in vivo. Healthy volunteers were examined for the velocity at which they metabolized sulfamethazine, and human liver cytosols were measured for NAT2 enzymatic activity, obtaining in vivo and in vitro metabolic phenotype, respectively. Typing of theNAT2gene was performed by polymerase chain reaction, restriction fragment length analysis, or allele-specific polymerase chain reaction. Multiple linear regression analysis provided quantitative relationships between allelic pattern and the NAT2 activities measured in vivo and in vitro. Estimates showed the influence of particular allelic configurations on enzyme activity in vitro and the extent of acetylation of the probe drug in vivo, resulting in a strict gene–dose effect. Comparison of in vitro results with in vivo phenotyping figures showed a high degree of correspondence, indicating that the one is the reflection of the other.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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4. |
Relation Between Dosage of Carbamazepine and Concentration in Hair and Plasma Samples From a Compliant Inpatient Epileptic Population |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 15-20
John Williams,
Philip Patsalos,
Zhang Mei,
Graham Schapel,
John Wilson,
Alan Richens,
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摘要:
Compliance is a problem in all areas of therapeutic medicine. Methods for its assessment are classified as either indirect or direct. Indirect assessment is based on criteria such as pill counts, questionnaires, and self-reporting; direct methods involve the analytic measurement of the drugs in biologic fluids such as plasma or urine. Drugs taken either therapeutically or recreationally become incorporated into hair. This prospective study investigated the relation between the daily intake of the antiepileptic drug carbamazepine and both its trough plasma and hair concentrations in a highly supervised inpatient population of patients with epilepsy during a period of 6 months. Results showed that although there was a significant variation between patients resulting from the substantial range in the daily intake of carbamazepine (800–2400 mg/day), the intrapatient variation in both trough plasma and hair concentrations during the 6-month period were not significantly different. The mean intrapatient percentage coefficient of variation in total plasma and hair concentrations of carbamazepine was 11.5 ± 4.7 and 15.0 ± 5.2, respectively, both of which were independent of the daily dosage. This relatively small intrapatient variation in hair concentration over time and its close relation to the plasma concentration suggests that hair analysis may be a complementary and useful technique in monitoring drug-taking behavior.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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5. |
Determination of Sildenafil Citrate in Plasma by High-Performance Liquid Chromatography and a Case for the Potential Interaction of Grapefruit Juice With Sildenafil Citrate |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 21-26
Miyoung Lee,
David Min,
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摘要:
This study was designed to establish a simple and reliable assay method that could be routinely used in the clinical laboratory setting using liquid extraction and high-performance liquid chromatography (HPLC). In addition, a case of potential interaction of grapefruit juice with sildenafil citrate is presented. The peaks of sildenafil (measured as sildenafil salt) and internal standard were identified with an ultraviolet detector at 230 nm and detection limit at 10 ng/mL. In a single elderly male patient, grapefruit juice increased the Cmaxof sildenafil by 42% (1067.7 ng/mL to 1517.0 ng/mL) although AUC was not significantly altered (4082.9 ng · h/mL to 4171.9 ng · h/mL) by grapefruit juice. Sildenafil could be determined in a simple and reliable method using HPLC with liquid extraction. This case indicated that grapefruit juice might increase the Cmaxof sildenafil without significant change in AUC. A further study with an appropriate number of subjects is needed before determining the degree of interaction between grapefruit juice and sildenafil.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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6. |
Bioanalysis of Racemic Reboxetine and Its Desethylated Metabolite in a Therapeutic Drug Monitoring Setting Using Solid Phase Extraction and HPLC |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 27-34
Daniel Öhman,
Björn Norlander,
Curt Peterson,
Finn Bengtsson,
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摘要:
Reboxetine is a new antidepressant drug acting as a potent and selective noradrenaline reuptake inhibitor on the noradrenergic neuronal system. Because of an expected interindividual variability in drug metabolism in the clinical practice the need for therapeutic drug monitoring routines in psychiatry is always a prominent feature. In this application, the preferred bioanalytic methodology was solid phase extraction combined with reversed-phase high-performance liquid chromatography and ultraviolet detection at 210 nm. The technique proved reliable, with interday and intraday variation of less than 5% and a quantification limit for reboxetine and one of its main metabolites O-desethylreboxetine (O-reboxetine) at 5 and 30 nmol/L, respectively. The method was applied on serum samples from 38 patients treated chronically with reboxetine. These samples were drawn as trough levels in steady state with a dosage range of 2–16 mg/day. They evidenced a mean reboxetine concentration that was fairly linear and dose proportional, although the variance in concentration was large between patients, even those taking the same dosage. O-reboxetine was detected in quantifiable amounts in only 1 of the 38 patients (<3%). In conclusion, these results suggest that a routine reboxetine therapeutic drug monitoring service that is robust enough to produce reliable and reproducible results may be introduced into everyday clinical practice.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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7. |
Mycophenolic Acid Plasma Concentrations: Influence of Comedication |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 35-38
Leonor Pou,
Merch Brunet,
Carme Cantarell,
Elena Vidal,
Frederic Oppenheimer,
Victor Monforte,
Jordi Vilardell,
Antonio Roman,
Jaume Martorell,
Luis Capdevila,
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摘要:
Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred forty transplant patients (kidney: 120 and lung: 20) received a triple immunosuppression regimen of CsA or TAC, prednisone and MMF. Twenty-two renal transplant patients received double therapy with MMF and prednisone. There was no correlation between MMF dose and MPA trough concentrations (r = -0.0657). The medians (range) of the MPA dose-to-concentration ratio (D/C) in the CsA and TAC groups were 0.90 (0.11–8.33) and 0.56 (0.11–14.3), respectively (p < 0.0001). According to the post transplant period (1–3, 4–6 and >6 months), D/C values were significantly lower in patients receiving MMF and TAC than those receiving MMF and CsA in all three periods. MPA levels in patients treated with MMF and CsA were significantly lower than those obtained in double therapy. The D/C ratio in CsA-treated patients, increased significantly (p = 0.0005) when CsA level increased. There was no relationship between D/C ratio and TAC blood concentrations.These results suggest that CsA exerts an influence on MPA trough levels, although further work is required to characterize the mechanism of interaction.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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8. |
Analytical Validation for a Series of Marker Compounds Used to Assess Renal Drug Elimination Processes |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 39-46
Andrew McLachlan,
Annette Gross,
Joanne Beal,
Ian Minns,
Susan Tett,
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摘要:
Renal drug elimination is determined by glomerular filtration, tubular secretion, and tubular reabsorption. Changes in the integrity of these processes influence renal drug clearance, and these changes may not be detected by conventional measures of renal function such as creatinine clearance. The aim of the current study was to examine the analytic issues needed to develop a cocktail of marker drugs (fluconazole,rac-pindolol, para-aminohippuric acid, sinistrin) to measure simultaneously the mechanisms contributing to renal clearance. High-performance liquid chromatographic methods of analysis for fluconazole, pindolol, para-aminohippuric acid, and creatinine and an enzymatic assay for sinistrin were developed or modified and then validated to allow determination of each of the compounds in both plasma and urine in the presence of all other marker drugs. A pilot clinical study in one volunteer was conducted to ensure that the assays were suitable for quantitating all the marker drugs to the sensitivity and specificity needed to allow accurate determination of individual renal clearances. The performance of all assays (plasma and urine) complied with published validation criteria. All standard curves displayed linearity over the concentration ranges required, with coefficients of correlation greater than 0.99. The precision of the interday and intraday variabilities of quality controls for each marker in plasma and urine were all less than 11.9% for each marker. Recoveries of markers (and internal standards) in plasma and urine were all at least 90%. All markers investigated were shown to be stable when plasma or urine was frozen and thawed. For all the assays developed, there were no interferences from other markers or endogenous substances. In a pilot clinical study, concentrations of all markers could be accurately and reproducibly determined for a sufficient duration of time after administration to calculate accurate renal clearance for each marker. This article presents details of the analytic techniques developed for measuring concentrations of marker drugs for different renal elimination processes administered as a single dose to define the processes contributing to renal drug elimination.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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9. |
Urine Drug Screens in Overdose Patients Do Not Contribute to Immediate Clinical Management |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 47-50
Rosalind Montague,
Robert Grace,
John Lewis,
Gillian Shenfield,
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摘要:
A prospective study assessed whether routine urine drug screens might alter the management of overdose patients. Urine was collected from 107 patients with a diagnosis of deliberate self-poisoning seen in the emergency department (ED) of a teaching hospital. The mean age of patients was 36 years (range 13–86 years) and 64% were female. All patients recovered after standard investigations and management, which did not include knowledge of urinary drug screen results. Two hundred ninety-seven compounds were detected in the 107 urine samples. Twenty percent were drugs administered in the ED. Sixty-five percent of patients were found to have taken more than one drug. Benzodiazepines were detected in 18% of samples, paracetamol in 10%, and alcohol in 8%. Sixty-one drugs, in 35 people, were identified that the patients did not report taking. Of these, paracetamol (10), benzodiazepines (9), and tetrahydrocannabinol (8) were the most common. All patients in whom paracetamol was found had already had paracetamol detected in blood and appropriate management instituted. If the results of urine screening had been immediately available this would not have affected the management or outcome of any patient.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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10. |
Fully Automated On-Line Determination of Olanzapine in Serum for Routine Therapeutic Drug Monitoring |
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Therapeutic Drug Monitoring,
Volume 23,
Issue 1,
2001,
Page 51-55
Ole Olesen,
Birgit Poulsen,
Kristian Linnet,
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摘要:
A method is presented for unattended fully automated extraction and on-line determination of the atypical antipsychotic drug olanzapine in serum. An ASPEC automatic sample-preparing apparatus with Isolute cyanopropyl-bonded silicagel cartridges was used for solid-phase extraction of the drugs from serum. The adsorbed drugs were eluted with methanol and an aliquot injected into a high-performance liquid chromatograph (HPLC) apparatus. Trifluoperazine was used as internal standard, and the analytes were separated on an unmodified silicagel column using methanol–ammonium acetate buffer pH 9.9 (85:15) as mobile phase. Ultraviolet detection at 257 nm was used for quantitation. Within the therapeutic range for the serum concentration of olanzapine, the interday variations for the quantitative determinations were <8%. Comparisons between concentrations measured using liquid–liquid extraction and the present on-line extraction method showed good agreement. Other drugs often used in combination with olanzapine did not interfere with the quantitative determinations. The method has been in routine use for more than 1 year for therapeutic drug monitoring.
ISSN:0163-4356
出版商:OVID
年代:2001
数据来源: OVID
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