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Biomedical subjects

T Buclin

Publications and source records attributed to T Buclin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients.

OBJECTIVES: To determine fluconazole population pharmacokinetics and explore the relationships between fluconazole average concentration and treatment effectiveness or microbiological resistance induction during a study aimed at evaluating the efficacy, tolerability and resistance induction after secondary prevention with fluconazole (150 mg weekly) versus placebo in human immunodeficiency virus-positive (HIV+) patients with oropharyngeal candidiasis. METHODS: Population pharmacokinetic parameters of fluconazole determined from 458 serum drug concentration measurements obtained over 37 months in 132 HIV + patients not receiving highly active antiretroviral therapy. Mean estimates and variabilities were generated using non-linear regression analysis. Logistic and linear regression analyses were used to explore the relationships between the estimated average concentration of fluconazole and candidiasis relapse or fungal resistance towards fluconazole. RESULTS: Fluconazole kinetics were best described by a one-compartment model with first-order oral absorp tion from the gastrointestinal tract. The pharmacokinetics were influenced only by body weight. No effect was observed for gender, age, height or lymphocyte CD4 counts. The mean apparent population clearance was 0.79 l/h, the volume of distribution 571 and the absorption constant (ka) 0.93 h(-1). Inter-occasion variability in clearance (45%) was large relative to intersubject variability (21%). Taking into account the average fluconazole concentration or the time above the minimal inhibitory concentrations did not clinically improve the prediction of the occurrence of oropharyngeal relapse or microbiological resistance. CONCLUSION: The relationship between fluconazole concentrations and preventive effectiveness was poor. Together with the rather large inter-occasion variability in fluconazole clearance, this suggests no role of therapeutic drug monitoring in optimising fluconazole treatment for secondary prevention.

AIDS-Related Opportunistic Infections↗
PubMed2001

Psychopharmacology in supportive care of cancer: a review for the clinician. IV. Other psychotropic agents.

Besides benzodiazepine, antidepressant and neuroleptic agents, all of which have established roles in supportive care, other psychotropic drugs deserve consideration in selected conditions affecting patients with advanced cancer. This article briefly reviews relevant aspects of miscellaneous psychotropics available for secondline treatment, including nonbenzodiazepine sedative, hypnotic and anxiolytic drugs, anaesthetic agents, stimulants, and analgesic adjuvants acting on the central nervous system. The proper use of such subsidiary psychotropic agents requires that both their specificities and the particular characteristics of palliative care patients are taken into account.

Anti-Anxiety Agents↗
PubMed2001

Rate, type, and cost of adverse drug reactions in emergency department admissions.

Background: Adverse drug reactions (ADRs) are a threat to patients' health and quality of life, and can generate significant expenses. They are generally underreported, with different rates in different health care systems. Methods: We conducted a 6-month survey of all primary admissions to the medical emergency department of a university hospital and assessed the rate, characteristics, avoidability, and marginal costs of ADRs. Results: A total of 7% of all admissions were mainly caused by ADRs. The most frequent were gastrointestinal bleeding (22.3%) and febrile neutropenia (14.4%). Anticancer drugs were involved in 22.7% of the cases, and anticoagulants, analgesics, and non-steroidal anti-inflammatory drugs in 8% each. Physicians had prescribed 70% of these drugs. Patients were predominantly treated in intermediate care units and ordinary wards. The mean cost per case amounted to CHF 3586+/-342, or a total of CHF 821204 over the 6-month-period (1 CHF=0.56 US$=0.87 Euro). A total of 67% were considered definitely imputable to drug effects and 32% were retrospectively regarded as avoidable. Conclusions: Interventions aimed at reducing the incidence of ADRs should be directed towards both patient education and physician training. This could save hospitals admissions and money, and could be used as an indicator of prescription quality.

Journal Article↗
PubMed2001

Nelfinavir plasma levels under twice-daily and three-times-daily regimens: high interpatient and low intrapatient variability.

Nelfinavir has been recently approved as a twice-daily (BID) dose regimen, but no evaluation of the influence of this regimen change on patients' protease inhibitor exposure has been published. The aim of this study was to compare trough plasma concentrations of nelfinavir obtained under the 1250-mg b.i.d regimen with the levels achieved with the original 750-mg three-times-daily (TID) regimen in 56 HIV-infected patients. Blood samples were obtained at steady state before the morning dose of nelfinavir. Plasma levels were measured by high-performance liquid chromatography. Eleven and 45 patients were following TID and BID regimens, respectively. Trough concentrations ranged from 0.14 to 11.74 mg/L and from 0.36 to 10.57 mg/L under TID and BID regimens, respectively. Large interpatient (coefficient of variation: 153%) and modest intrapatient (45%) variabilities of nelfinavir levels were observed. Twenty-one patients (38%) and six patients (11%) had levels above and below, respectively, the trough nelfinavir range (1.0--3.0 mg/L) recommended by the manufacturer. Trough levels are not affected by the dosing regimen; they mainly reflect the important interindividual variability, while remaining fairly stable over time. Many subjects had plasma levels repeatedly outside the assumed therapeutic range. Dose adjustment based on therapeutic drug monitoring may contribute to optimizing antiretroviral therapy.

Adult↗
PubMed2001

Disappearance rate of catecholamines, total metanephrines, and neuropeptide Y from the plasma of patients after resection of pheochromocytoma.

BACKGROUND: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value. METHODS: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration-time curve over 120 min. RESULTS: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 +/- 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated. CONCLUSIONS: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.

Catecholamines↗
PubMed2000

Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir, nelfinavir and the non-nucleoside reverse transcriptase inhibitor efavirenz by high-performance liquid chromatography after solid-phase extraction.

As part of an on-going study on the suitability of a formal therapeutic drug monitoring (TDM) of antiviral drugs for improving the management of HIV infection, a high-performance liquid chromatography method has been developed to quantify simultaneously in plasma five HIV protease inhibitors (PIs) (i.e., indinavir, amprenavir, saquinavir, ritonavir, nelfinavir) and the novel non-nucleoside reverse transcriptase inhibitor efavirenz. After viral inactivation by heat (60 degrees C for 60 min), plasma (600 microl), with clozapine added as internal standard, is diluted 1:1 with phosphate buffer, pH 7 and subjected to a solid-phase extraction on a C18 cartridge. Matrix components are eliminated with 2 x 500 microl of a solution of 0.1% H3PO4 neutralised with NaOH to pH 7. PIs and efavirenz are eluted with 3 x 500 microl MeOH. The resulting eluate is evaporated under nitrogen at room temperature and is reconstituted in 100 microl 50% MeOH. A 40-microl volume is subjected to HPLC analysis onto a Nucleosil 100, 5 microm C18 AB column, using a gradient elution of MeCN and phosphate buffer adjusted to pH 5.15 and containing 0.02% sodium heptanesulfonate: 15:85 at 0 min-->30:70 at 2 min-->32:68 at 8 min-->42:58 at 18 min-->46:54 at 34 min, followed by column cleaning with MeCN-buffer, pH 5.15 (90:10), onto which 0.3% AcOH is added. Clozapine, indinavir, amprenavir, saquinavir, ritonavir, efavirenz and nelfinavir are detected by UV at 201 nm at a retention time of 8.2, 13.0, 16.3, 21.5, 26.5, 28.7 and 31.9 min, respectively. The total run time for a single analysis is 47 min, including the washing-out and reequilibration steps. The calibration curves are linear over the range 100-10,000 ng/ml. The absolute recovery of PIs/efavirenz is always higher than 88%. The method is precise with mean inter-day relative standard deviations within 2.5-9.8% and accurate (range of inter-day deviations -4.6 to +4.3%). The in vitro stability of plasma spiked with PIs/efavirenz at 750, 3000 and 9000 ng/ml has been studied at room temperature, -20 degrees C and +60 degrees C. The method has been validated and is currently applied to the monitoring of PIs and efavirenz in HIV patients. This HPLC assay may help clinicians confronted to questionable compliance, side effects or treatment failure in elucidating whether patients are exposed to adequate circulating drug levels. The availability of such an assay represents an essential step in elucidating the utility of a formal TDM for the optimal follow-up of HIV patients.

Alkynes↗
PubMed2000

Bioavailability of repeated oral administration of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase in healthy volunteers.

BACKGROUND: MDL 100,240 (pyrido[2,1-a] [2]benzazepine-4-carboxylic acid,7-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-1,2,3,4,6,7,8, 12b-octahydro-6-oxo, [4S-[4alpha,7alpha(R(*)),12bbeta]]-) is a molecule possessing an inhibiting ability on both angiotensin converting enzyme (ACE) and neutral endopeptidase, the enzyme responsible for atrial natriuretic peptide (ANP) degradation. Such a dual mechanism of action presents a potential clinical interest for the treatment of hypertension and congestive heart failure. OBJECTIVES: To evaluate the bioavailability of MDL 100,240 and its accumulation over repeated oral administration, using ACE inhibition as a surrogate for plasma drug level and determining its profile after oral and i.v. administration. METHODS: First, in an open, one-period, single-dose study, the ACE inhibition profile was characterised following a 12.5 mg MDL 100,240 i.v. infusion. Second, in a three-group, parallel, randomised, double-blind study, each group of four subjects received q.d., over 8 days, 2.5, 10 or 20 mg of MDL 100,240 orally. The ACE inhibition profile was determined on day 1 and day 8. Trough plasma ACE was measured on days 2, 3 and 4. The recovery of ACE activity was monitored up to 72 h after the last dose of MDL 100,240. RESULTS: ACE inhibition profile was similar on day 1 and day 8, and trough inhibition remained unchanged after the 8 days of treatment with 10 mg or 20 mg. Following repeated 2.5-mg ingestion, trough inhibition increased from 33% to 44% after the eighth dose. The oral bioavailability of MDL 100,240 was estimated at 85%, not statistically different from 100%. The accumulation ratio at steady state was estimated at 112%. Expressing the accumulation ratio in terms of half-life, a t(1/2) of 0.31 days or 7. 5 h was estimated. CONCLUSION: MDL 100,240 (oral solution) has a good bioavailability, as estimated by ACE inhibition, and no drug accumulation seems to occur over 8 days with the 10-mg and 20-mg doses, but a slight rise in the trough level is observed with the 2. 5-mg dose.

Administration, Oral↗
PubMed2000

Psychopharmacology in supportive care of cancer: a review for the clinician. III. Antidepressants.

This review covers pharmacokinetics, adverse effects and drug interactions of antidepressants and the indications for them, with the aim of assisting the clinician working in palliative and supportive care in the prescription of such drugs. Practical considerations and decision trees to be used prior to the prescription of an antidepressant are also part of this review. Special emphasis is put on the management of depression, which is frequent in patients with advanced cancer and often remains underdetected and undertreated, or is treated at a stage when there is little time for medication to have an effect.

Antidepressive Agents↗
PubMed2000

Psychopharmacology in supportive care of cancer: a review for the clinician: II. Neuroleptics.

Neuroleptics are frequently used in patients with advanced cancer. Most relevant and practical aspects of their use in supportive cancer care are reviewed, to assist the clinical oncologist and palliative care specialist when prescribing these drugs. This article reviews pharmacological properties, indications, such as delirium, nausea and vomiting, pain, anxiety and other symptoms, adverse effects, and drug interactions of neuroleptics and compares the profiles of different compounds. Special emphasis is put on the role of neuroleptics in the management of delirium.

Antipsychotic Agents↗
PubMed2000

Pharmacokinetics and pharmacodynamics of IFN-beta 1a in healthy volunteers.

The pharmacokinetics of recombinant human interferon-beta1a (IFN-beta1a) (Rebif, Ares-Serono, Geneva, Switzerland) were investigated in healthy volunteers following intravenous (i.v.) administration of increasing single doses of the drug (22 microg/6 million international units [MIU], 44 microg/12 MIU, and 66 microg/18 MIU); i.v., intramuscular (i.m.), and subcutaneous (s.c.) administration of a 66-microg dose; and repeated s.c. administration of four 66-microg doses at 48-h intervals. The disposition of IFN-beta1a followed triexponential decay after i.v. administration (half-lives 3 min, 42 min, and 22 h, respectively). After s.c. and i. m. administration, absorption was the rate-limiting factor in the terminal phase. The median absolute bioavailabilities were 30% and 27%, respectively. The accumulation ratio after repeated s.c. injections was 2.4, and a terminal half-life of 66 h was observed. Intracellular 2-5A synthetase activity and serum neopterin and beta2-microglobulin concentrations increased after all IFN-beta1a injections and remained elevated following every-other-day administration. The local tolerance was good, and the systemic tolerance was satisfactory.

Adolescent↗
PubMed1999

Influence of interferon beta-1a dose frequency on PBMC cytokine secretion and biological effect markers.

Interferon-beta regimens for immune-mediated diseases, such as multiple sclerosis (MS), have not been compared regarding their biological effects. In this randomized, parallel-group, placebo-controlled study, cytokine secretion by mitogen-stimulated PBMCs and serum response markers were assessed in volunteers receiving subcutaneous recombinant IFN beta-1a (Rebif, Ares-Serono) 22 microg once a week (QW), 22 microg three times a week, 66 microg QW, or placebo. The production of IL-1beta, IL-6, IFN-gamma, TNF-alpha and TNF-beta markedly decreased during 24-48 h after each injection, with limited dose-dependency and no evidence of tolerance or effect augmentation over 1 month. IL-10 secretion remained unchanged. The increase in serum beta2-microglobulin, neopterin and 2-5A-synthetase was more sustained. Thus, IFN-beta-induced immunomodulation in vivo strongly depends on the administration schedule, the time-integrated effect being 2-3 times greater when a same weekly dose is divided in three injections.

2',5'-Oligoadenylate Synthetase↗
PubMed1999

[The medical advisor: a friend to count on?].

The medical advisor can be helpful for the practitioner as a source of information on drugs. However, the physician has to learn how to obtain basic rational information on therapy, how to identify whether the given information is relevant or not for the clinical decision, to distinguish between rational and irrational information during presentation and to validate all given information.

Consultants↗
PubMed1999

Trace lithium in mood disorders.

BACKGROUND: Variations in trace (endogenous) lithium exchanges have been postulated to play a role in the pathophysiology of affective diseases. This prospective study aimed to check whether plasma, erythrocytes and urine trace lithium levels were altered in mood disorders. METHODS: Trace lithium was determined by atomic absorption spectrophotometry in patients without mood stabilizing drugs or somatic diseases, hospitalized for bipolar affective disorders, major depressive episodes, and other psychiatric disorders with depressive features. Patients admitted for psychotic disorders without mood alterations and healthy volunteers served as controls. RESULTS: There were no differences in trace lithium status between the groups. Erythrocytes/plasma ratios appeared higher than described on therapeutic lithium (1.6+/-0.7, N = 199). LIMITATIONS: The study had sufficient power to detect clinically significant differences in whole body lithium handling between the groups. However, it did not address alterations of lithium exchanges across neuronal membranes or the blood-brain barrier. CONCLUSIONS: Alterations of membrane exchanges hypothetically associated with mood disorders are not reflected in plasma or erythrocytes trace lithium levels. The occurrence of mood disorders seems not to be related to abnormalities in endogenous lithium.

Antimanic Agents↗
PubMed1999

The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: a randomized double-blind controlled trial.

BACKGROUND: Dyspnea represents a very frequent and distressing symptom in patients with advanced cancer. This study was undertaken to assess the efficacy of morphine on dyspnea and its safety for ventilatory function in elderly advanced cancer patients. PATIENTS AND METHODS: Nine elderly patients with dyspnea due to lung involvement were randomized to receive either morphine subcutaneously (5 mg in seven opioid-naïve patients and 3.75 mg in two patients on top of their regular oral dose of 7.5 mg q4 h) or placebo on day 1. On day 2, they were crossed over to receive the alternate treatment. Dyspnea was assessed every fifteen minutes using a visual analogue scale (VAS: 0-100 mm) and the ordinal scale developed by Borg (0-10 points). Pain, somnolence and anxiety were assessed using VAS. Respiratory effort, respiratory rate and oxygen saturation were also measured repeatedly. RESULTS: Mean changes in dyspnea 45 minutes after injection were -25 +/- 10 mm and -1.2 +/- 1.2 points for morphine, versus 0.6 +/- 7.7 mm (P < 0.01) and -0.1 +/- 0.3 points (P = 0.03) for placebo on VAS and Borg scale, respectively. No relevant changes were observed in somnolence, pain, anxiety, respiratory effort and rate, and oxygen saturation. CONCLUSIONS: Morphine appears effective for cancer dyspnea, and it does not compromise respiratory function at the dose level used.

Aged↗
PubMed1999

Evaluation of noninvasive blood pressure recording by photoplethysmography in clinical studies using angiotensin challenges.

AIMS: Continuous noninvasive blood pressure measurement by photoplethysmography has been regularly used in the experimental paradigm of angiotensin challenges, applied to the phase I clinical testing of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. This work aims to evaluate the performance of this measurement method, in terms of reliability, reproducibility and dependence on technical settings. METHODS: Data have been gathered from 13 clinical studies on antihypertensive drugs, using the Finapres device for measuring the response to exogenous angiotensin challenges. The agreement between simultaneous recordings at different fingers and the influence of the reading method are assessed. A literature review addresses the question of the concordance between results obtained noninvasively and through arterial cannulation. RESULTS: The relative precision of blood pressure monitoring by photoplethysmography allows reproducible determination of angiotensin-induced blood pressure peaks (agreement limits for systolic and diastolic peaks: 12 and 6 mmHg respectively). The reading method influences the results to a similar extent. As compared with blood pressure measured intra-arterially, the difference is usually within limits of clinical acceptability. CONCLUSIONS: In the context of phase I studies using the angiotensin challenges methodology, the reliability and reproducibility of noninvasive blood pressure measurement appear satisfactory, despite the technical limitations of this method. The impact of selected changes in the settings and reading methods is limited.

Angiotensin II↗