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Biomedical subjects

E Rey

Publications and source records attributed to E Rey.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile neutropenia: a prospective study.

BACKGROUND: We hypothesized that cancer-related inflammation might increase the risk of febrile neutropenia (FN) induced by docetaxel (DCX, Taxotere), by both affecting the exposure to DCX and the tissue sensitivity. PATIENTS AND METHODS: Advanced cancer patients with normal liver function, performance status (PS)<3, were included. Cytochrome P450 3A (CYP 3A) activity was estimated before the first cycle of DCX by a single determination of midazolam plasma concentration, 4 hours after 0.015 mg/kg i.v. bolus. Following the first cycle of 75-100 mg/m2 DCX, clearance and area under the concentration versus time curve (AUC) were estimated using a limited sampling strategy. RESULTS: Among 56 assessable patients, 7 FNs occurred after first cycle (13%). In univariate analysis, high midazolam concentration and free DCX AUC were associated with severe neutropenia and FN. In addition to DCX exposure-related parameters, the risk of FN was also correlated with poor PS, baseline lymphopenia and lung cancer, while high ferritin level, indicator of an inflammatory state, reached borderline significance (P=0.07). By multivariate analysis, total DCX AUC and baseline lymphopenia were associated with FN. High midazolam concentration was correlated with elevated ferritin level (r=0.32; P=0.02). CONCLUSION: Inflammatory status and lymphocyte count should be included in the evaluation of the benefice/risk ratio before the initiation of DCX.

Aged↗
PubMed2006

Pharmacokinetics and toxicity of docetaxel: role of CYP3A, MDR1, and GST polymorphisms.

OBJECTIVE: Patients initiating docetaxel chemotherapy were genotyped for CYP3A4, CYP3A5, MDR1, GSTM1, GSTT1, GSTM3, and GSTP1 to identify variability factors of docetaxel pharmacokinetics and toxicity. METHODS: Genotyping was performed by direct sequencing (CYP3A4), real-time polymerase chain reaction (CYP3A5), and polymerase chain reaction-restriction fragment length polymorphism (MDR1 and GST). The clearance and area under the curve of docetaxel were calculated by use of a Bayesian approach. Absolute neutrophil count was recorded twice weekly. RESULTS: With regard to the pharmacokinetic analysis, 58 patients were included. CYP3A4*1B carriers (*1A/*1B, n=4), who are also CYP3A5*1/*3 carriers, had a significantly higher clearance and lower dose-normalized area under the curve of docetaxel than those with the wild genotype (*1A/*1A, n=53): 55.2+/-13.5 L/h versus 37.3+/-11.7 L/h (P=.01) and 31.4+/-6.2 (microg . h/L)/(mg/m(2)) versus 52.7+/-18.2 (microg . h/L)/(mg/m(2)) (P=.005), respectively. No influence of MDR1 was evidenced. With regard to the pharmacodynamic analysis, febrile neutropenia occurred more frequently in GSTP1*A/*B carriers (31.6% versus 3.7% in *A/*A carriers and 0% in *A/*C, *B/*B, and *B/*C carriers) (P=.037). Grade 3 neutropenia occurred more frequently in 3435TT MDR1 genotype carriers: TT, 100%; CT, 77.3%; and CC, 54.5% (P=.046). No influence of GSTM1, GSTT1, or GSTM3 polymorphisms was evidenced on docetaxel toxicity. CONCLUSIONS: Patients carrying the CYP3A*1B allele may have enhanced docetaxel clearance and may be underexposed, whereas those carrying GSTP1*A/*B and 3435TT genotypes may have excessive hematologic toxicity. Further studies are warranted to determine the usefulness of genotyping before docetaxel treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Use of antisecretory drugs among consumers of non-steroidal anti-inflammatory drugs in the general population.

BACKGROUND: Overall success of prophylactic strategies against non-steroidal anti-inflammatory drug (NSAID) complications depends on the use of gastroprotective drugs. AIM: We examined the use of antisecretory drugs in NSAID users in the general population of Spain. PARTICIPANTS AND METHODS: In 2002, a phone interview was conducted with 2500 persons representative of the general population of Spain. Using a validated questionnaire, we asked about the use of NSAID, aspirin and antisecretory drugs, and history of digestive diseases. We estimated the use of antisecretory drugs in NSAID users, according to risk factors for gastrointestinal (GI) lesions associated with NSAID. RESULTS: In total, 425 persons [17.0% (95% CI 15.5-18.5%)] were NSAID users. Of them, 69 persons (16.2%; 95% CI 12.7-19.7%) used antisecretory drugs [proton pump inhibitor (PPI) 11.8% and H2-blocker 4.9%]. Forty-four of the 224 NSAID users (19.6%) with one risk factor for GI lesions were antisecretory drug users (PPI 16%; H2-blocker 4%), compared with 24 of the 197 NSAID users (12.7%) without risk factors (PPI 6.6%; H2-blocker 6.1%). NSAID users with risk factors for GI lesions but without upper GI (UGI) symptoms did not consume more antisecretory drugs than equivalent non-NSAID users (12.9% vs. 10.7%). CONCLUSION: Current strategies to prevent GI lesions in NSAID users are not effective from a population perspective, especially in subjects without UGI symptoms.

Adult↗
PubMed2006

Impact of gastroesophageal reflux symptoms on health resource usage and work absenteeism in Spain.

OBJECTIVES: To estimate the impact of gastroesophageal reflux (GER) symptoms on the utilization of healthcare services and work absenteeism in Spain. METHODS: A cross-sectional study on 2,500 subjects representative of the Spanish population from 40 to 79 years of age. Data were collected via a telephone interview in January 2002 using Locke s questionnaire after its cross-cultural adaptation and validation for telephone use in Spain. RESULTS: GER is responsible for 296.8 doctor consultations (95% CI: 245.3-348.7) per 1,000 inhabitants per year, for 24 esophagogastrointestinal radiographic studies per 1,000 inhabitants per year (95% CI: 18-30), for 32.4 (95% CI: 25.5-39.3) high digestive endoscopies per 1,000 inhabitants per year, and for the loss of 201 (95% CI: 0-411.1) working days per 1,000 employed inhabitants with GER per year. In relation to medication intake, GER resulted in 4,092 (95% CI: 3,300-5,133) treatment days with H2 antagonists per 1,000 inhabitants per year, 9,030 (95% CI: 7,846-10,332) treatment days with proton pump inhibitors per 1,000 inhabitants per year, and 1,082 (95% CI: 519-1,549) treatment days with prokinetics per 1,000 inhabitants per year. CONCLUSIONS: GER has a large impact on the utilization of healthcare resources and work absenteeism in Spain, in contrast to the widespread belief that it is an illness of little importance.

Absenteeism↗
PubMed2005

Weight related differences in the pharmacokinetics of abacavir in HIV-infected patients.

AIM: To study the possible influence of patient characteristics on abacavir pharmacokinetics. METHODS: A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM. RESULTS: Abacavir pharmacokinetics was well described by a two-compartment open model with linear absorption and elimination. Typical population estimates for the absorption rate constant (Ka), the apparent central distribution volume (Vc/F), the apparent peripheral distribution volume (Vp/F), the apparent intercompartmental clearance (Q/F) and the apparent plasma clearance (CL/F) were 1.8 h(-1), 75 l, 23.6 l, 10 l h(-1) and 47.5 l h(-1), respectively. Apparent plasma clearance was positively related to bodyweight. Individual Bayesian estimates of CL/F were used to calculate abacavir AUC. The latter decreased from 10.7 +/- 5.0 to 5.7 +/- 1.6 mgh l(-1) when bodyweight increased from 36 to 102 kg. This drop in abacavir exposure could lead to suboptimal treatment for the heaviest patients, as antiviral efficacy of abacavir is known to be related to its AUC. A 400 mg abacavir dose would be necessary to achieve adequate exposure to abacavir in patients weighing more than 60 kg. CONCLUSIONS: The apparent plasma clearance of abacavir was positively related to bodyweight. The efficacy of the current recommended abacavir dosage for patients with high bodyweight should be evaluated in further studies.

Administration, Oral↗
PubMed2005

Dose-finding study of ibuprofen in patent ductus arteriosus using the continual reassessment method.

OBJECTIVE: Intravenous ibuprofen (IBU) has been found to be as effective as indomethacin for the treatment of patent ductus arteriosus (PDA) in preterm infants and has been associated with fewer adverse effects in comparative phase III studies. The dose regimen used (10-5-5 mg/kg/day) was based on limited pharmacokinetic data and no phase II study was available to determine the optimal dose of IBU for this indication. The present study was designed to determine the minimum effective dose regimen (MEDR) of IBU (one course) required to close ductus arteriosus in preterm infants. METHOD: A double-blind dose-finding study was conducted using the continual reassessment method, a Bayesian sequential design. Two distinct target closure rates were initially chosen according to postmenstrual age (PMA) at birth: 80% in infants with a PMA of 27-29 weeks, and 50% in infants with a PMA < 27 weeks. Forty neonates (20 in each PMA group) with PDA were treated between days 3 and 5 of life. Four different dose regimens were tested: loading doses of 5, 10, 15 or 20 mg/kg, followed by two doses (1/2 loading dose) at 24-h intervals. Efficacy was evaluated by echocardiography 24 h after the third infusion. RESULTS: In infants with a PMA of 27-29 weeks, the estimated MEDR was 10-5-5 mg/kg with a final estimated probability of success of 77% (95% credibility interval: 56-92%). The 15-7.5-7.5 mg/kg dose regimen had a better estimated probability of success (88%, 95% credibility interval: 68-97%), but resulted in more minor renal adverse effects. In contrast, in infants with a PMA < 27 weeks, the estimated MEDR was 20-10-10 mg/kg with an estimated probability of success of 54.8% (95% credibility interval: 22-84%), whereas the conventional dose regimen resulted in a low estimated probability of success (30.6%, 95% credibility interval: 13-56%). In these infants, compared with those with a PMA of 27-29 weeks, minor renal adverse effects were more frequent from the 10-5-5 mg/kg/day dose regimen and did not appear to be clearly dose related. CONCLUSION: This study confirms that the currently recommended dose regimen (10-5-5 mg/kg) of IBU is associated with a high closure rate (80%) and few adverse effects in premature infants with a PMA of 27-29 weeks. The failure rate was much higher below 27 weeks. A higher dose regimen (20-10-10 mg/kg) might achieve a higher closure rate. However, tolerability and safety of this dose regimen should be assessed in a larger population before considering the use of these doses for ductus arteriosus closure.

Bayes Theorem↗
PubMed2005

Minimum effective dose of midazolam for sedation of mechanically ventilated neonates.

OBJECTIVE: To determine the minimal effective dose (MED) of intravenous midazolam, required for appropriate sedation in 95% of patients, 1 h after drug administration. METHODS: A double-blind dose-finding study using the continual reassessment method, a Bayesian sequential design. Twenty-three newborn infants hospitalized in intensive care unit participated. Inclusion criteria were: (i) post-natal age <28 days, (ii) gestational age >33 weeks, (iii) intubation and ventilatory support required for respiratory distress syndrome, (iv) need for sedation (i.e. one of the six following criteria: agitation or grimacing or crying facial expression before tracheal suctioning, agitation or grimacing or crying facial expression during tracheal suctioning). Each neonate was allocated to a loading dose, ranging from 75 to 200 microg/kg, and a maintenance dose ranging from 37.5 to 100 microg/kg/h. RESULTS: The primary endpoint was the level of sedation 1 h after the onset of infusion. The sedation procedure was classified as a success if all the following clinical criteria were met: no agitation, no grimacing and no crying facial expression before as well as during tracheal suctioning. Based on the 23 patients, the final estimated probability of success was 76.9% (95% credibility interval: 56.6-91.4%) for the 200 microg/kg loading dose. no significant adverse effect was observed. CONCLUSIONS: Continual reassessment is a new approach, suitable for dose-finding study in neonates. this method overcomes some of the ethical, statistical and practical problems associated with this population. Using this method, the MED was estimated to be the 200 mug/kg loading dose of midazolam.

Dose-Response Relationship, Drug↗
PubMed2005

Quinine pharmacokinetics and pharmacodynamics in children with malaria caused by Plasmodium falciparum.

The aim of the present study was to assess the pharmacokinetics and the efficacy of a shorter than usual 5-day quinine treatment given orally to children in Cameroon with malaria caused by Plasmodium falciparum. Quinine (8.3 mg of base per kg of body weight every 8 h) was administered as a 2% formiate salt syrup for 5 days to 30 children (age range, 0.55 to 6.7 years) with uncomplicated falciparum malaria (initial parasitemia, 1.4 x 10(3) to 1.8 x 10(5)/microl). Quinine concentrations in plasma samples (five to nine per patient) were measured by liquid chromatography on days 1 to 3. Parasitemia was counted on days 0, 1, 2, 3, 4, 7, and 14. Pharmacokinetic and pharmacodynamic data were analyzed by population approaches by using NONMEM and WinBugs, respectively. The kinetics of quinine were best described by a one-compartment model with time-varying protein binding. Clearance and the volume of distribution were positively correlated with body weight and increased over time. Parasitemia was undetectable from day 3 to 14 in all children. The time to a 4-log reduction of the initial level of parasitemia (Ter) was related to the average quinine concentration from 0 to 72 h (Cav) as Ter = Tmin [1 + (C50/Cav)s], where sigmoidicity (s) is equal to 2, Tmin is the time to eradication at infinite Cav, and C50 is the value of Cav for which Ter is twice Tmin. The C50 distribution was unimodal, and all C50 values were less than 8 mg/liter, while Cav ranged from 5.9 to 18.3 mg/liter. The median (10th to 90th percentile) Ter was 47 h (range, 39 to 76 h). The efficacy of a 5-day treatment course should be evaluated in a larger clinical trial.

Administration, Oral↗
PubMed2005

Has the identification of rectal hypersensitivity any implication in the clinical outcome of irritable bowel syndrome?

BACKGROUND: Sixty percent of patients with irritable bowel disease (IBS) are hypersensitive to rectal distension. It is uncertain to what extend the identification of this abnormality has an impact in the clinical outcome. OBJECTIVE: to evaluate if rectal hypersensitivity is associated with a different clinical outcome, prognosis and use of medical resources. MATERIAL AND METHODS: Patients with IBS (Rome II criteria) who underwent a rectal distension study at least one year before were eligible if they have not been included in any research protocol since then. We reviewed how many times in the last year they came to emergency room, underwent an endoscopy, and consulted a gastroenterologist or other medical physician for any reason. Also, a telephone interview was done by a gastroenterology fellow using a structured questionnaire to evaluate the frequency and severity of their symptoms in the last year and last month. RESULTS: A total of 52 patients were eligible and 38 were included. Fourteen were not included because inability to made a phone contact or did not consent to phone interview. Twenty six patients were hypersensitive and 12 normosensitive. Both groups had similar symptoms (frequency and severity) but hypersensitive patients visited less to the gastroenterologist (1.2 +/- 0.2 vs. 2.9 +/- 0.6 times yearly, p < 0.01). CONCLUSION: Identification of rectal hypersensitivity to distension is associated to less consultation to gastroenterologist, although severity and frequency of symptoms are not modified. Finding of an objective explanation of the symptoms seems to help patients to understand their disease, leading to a decrease in resources use.

Adult↗
PubMed2004

Effects of effervescent ranitidine on gastric pH: comparison with almagate and placebo in fasting and postprandial conditions.

AIM: To compare the effect of effervescent ranitidine, almagate (magnesium carbonate-aluminium hydroxide) and placebo on gastric pH, in fasting and postprandial conditions. METHODS: Twelve healthy volunteers underwent a gastro-oesophageal pH monitoring on three different occasions after the administration of each of the following randomly allocated treatments: almagate, effervescent ranitidine and placebo. Treatment effects were assessed in fasting and postprandial conditions. Onset and duration of alkalinization, percentage of time with pH > 4 and median gastric pH after treatments were calculated in both periods. RESULTS: Onset of action of effervescent ranitidine was similar to almagate in fasting [median 1.2 min (IQR: 0.6-12.7) vs. 2.9 min (0.4-227.6)] and postprandial conditions [1.4 min (0.5-4.9) vs. 4.1 min (1.3-63.8)] and both were significantly faster than placebo [fasting 211.1 min (2.7-240); postprandial 240 min (175.6-240)]. The duration of action of effervescent ranitidine was statistically significant longer than almagate in fasting [235 min (105.2-239.4) vs. 19.4 min (6.7-38.8)] and postprandial conditions [171.8 min (133.2-239.5) vs. 61.3 min (44.7-91.9)]. Effervescent ranitidine was more effective than almagate in increasing the percentage of time with a pH > 4 both in fasting (73.9% vs. 7.3%) and postprandial (59.1% vs. 21.3%). CONCLUSIONS: Effervescent ranitidine shows an effect on gastric pH as fast as almagate but provides a duration of alkalinization longer than almagate, in both fasting and postprandial conditions.

Adult↗
PubMed2004

Assessment of cetirizine, an antihistamine, to prevent cutaneous reactions to nevirapine therapy: results of the viramune-zyrtec double-blind, placebo-controlled trial.

We conducted a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of cetirizine to assess the ability of antihistamines to prevent nevirapine-associated rash in patients infected with human immunodeficiency virus type 1. Patients initiating treatment with nevirapine were randomized to receive either cetirizine, 10 mg q.d. (104 patients), or placebo (96 patients) during the first 6 weeks of therapy. Rash occurred in 22 (11%) of 200 patients; 10 (9.6%) were in the cetirizine group and 12 (12.5%) were in the placebo group (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.31-1.81; P=.5). Five of 22 rashes were cases of hypersensitivity syndrome. The rate of nevirapine discontinuation due to rash was similar in the 2 groups (7.7% and 6.25% in the cetirizine and placebo groups, respectively; P=.4). Multivariate analysis showed no treatment-group effect but indicated that age >40 years (OR, 3.83; 95% CI, 1.4-10.46; P=.008) was associated with an increased risk of rash. Cetirizine has no preventive effect on nevirapine-associated rash.

Adult↗
PubMed2004

Symptoms of gastro-oesophageal reflux: prevalence, severity, duration and associated factors in a Spanish population.

AIM: To measure the prevalence of gastro-oesophageal reflux symptoms and to identify associated factors in a representative sample of the Spanish population. METHODS: A telephone survey of 2500 subjects was performed using a validated questionnaire. The association of gastro-oesophageal reflux symptoms (defined as the presence of heartburn or acid regurgitation) and their clinical characteristics with potential risk factors was summarized using the odds ratios (OR) obtained by multiple logistic regression. RESULTS: The response rate was 71.2%. The annual prevalence of gastro-oesophageal reflux symptoms was 31.6% [95% confidence interval (CI), 29.8-33.4] and the weekly prevalence was 9.8% (95% CI, 8.6-10.9). Gastro-oesophageal reflux symptoms were associated with excess weight (OR, 1.53; 95% CI, 1.23-1.92), obesity (OR, 1.74; 95% CI, 1.30-2.32), the psychosomatic symptom score (OR, 2.98; 95% CI, 2.41-3.67) and the presence of gastro-oesophageal reflux symptoms in a direct family member (OR, 1.61; 95% CI, 1.17-2.23). Gastro-oesophageal reflux symptoms of > or =10 years' duration were more frequent in obese subjects (OR, 1.92; 95% CI, 1.14-3.22) and those with a direct family member with gastro-oesophageal reflux symptoms (OR, 2.42; 95% CI, 1.44-4.06). Factors associated with gastro-oesophageal reflux symptoms of < or =1 year duration were a spouse with gastro-oesophageal reflux symptoms (OR, 2.33; 95% CI, 1.39-3.9) and the consumption of 1-5 aspirins/week (OR, 1.70; 95% CI, 1.01-2.86). CONCLUSIONS: The prevalence of frequent gastro-oesophageal reflux symptoms in Spain is lower than that observed in other Western populations. The psychosomatic symptom score is the factor most strongly associated with gastro-oesophageal reflux symptoms. Long-term gastro-oesophageal reflux symptoms are associated with certain genetic factors (obesity, family history of gastro-oesophageal reflux symptoms), whereas short-term gastro-oesophageal reflux symptoms are associated with factors of probable environmental nature.

Adult↗