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Biomedical subjects

X Carné

Publications and source records attributed to X Carné.

At least 19 recordsLinked to original sources
PubMed2004

Penetration of linezolid into the anterior chamber (aqueous humor) of the human eye after intravenous administration.

We determined the linezolid concentrations in serum samples and aqueous humors (AHs) from 21 patients undergoing cataract extraction. Cataract removal was performed at various times (from 60 to 270 min) after the end of a 30-min infusion of 600 mg of linezolid. Serum samples were obtained 1 h after the end of linezolid administration to determine the maximum concentration of linezolid (C(max)); AHs and a second serum sample were taken simultaneously during the operation, and the concentrations of linezolid in AH (C(AH)) and serum (C(S)) were determined. The mean C(AH) 1 h after linezolid administration was 4.94 micro g/ml, and the mean ratio of C(AH) to C(S) (R = C(AH)/C(S)) was 0.43. All patients had a C(AH) of >2 micro g/ml, which was higher than the MIC at which 90% of Staphylococcus epidermidis strains are inhibited.

Acetamides↗
PubMed2001

Determination of efavirenz in human plasma by high-performance liquid chromatography with ultraviolet detection.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor for the treatment of the HIV infection. A simple, high-performance liquid chromatographic method has been developed and validated for the quantitative determination of efavirenz in human plasma. The method involved solid-phase extraction of the drug and the internal standard (L-737,354) from 300 microl of human plasma. The analysis was via UV detection at 250 nm using a reversed-phase C8 analytical column and a isocratic mobile phase consisting of phosphate buffer (pH 5.75)-acetonitrile that resolved the drug and internal standard from endogenous matrix components and potential coadministered drugs. Within- and between-day precisions were less than 8.6% for all quality control samples. The lower limit of quantification was 0.1 microg/ml. Recovery of efavirenz from human plasma was greater than 83%. This validated assay is being used in pharmacokinetic studies with efavirenz.

Alkynes↗
PubMed2001

Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.

OBJECTIVES: To assess the incidence and risk factors for hepatotoxicity associated with nevirapine. DESIGN: A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000. METHOD: Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values. RESULTS: Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity. CONCLUSIONS: Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.

Adult↗
PubMed2001

Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.

A rapid, simple and sensitive high-performance liquid chromatographic (HPLC) assay has been developed for the simultaneous quantification of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma. The method involved the solid-phase extraction of the five drugs and the internal standard (I.S., verapamil) from 400 microl of human plasma. The HPLC analysis used a reversed-phase C18 analytical column and a mobile phase consisting of a gradient with 15 mM phosphate buffer (pH 5.75)-acetonitrile and UV monitoring. The method was linear over the therapeutic concentration range for the five HIV-protease inhibitors. The accuracy of the method ranged from 98.2 to 106.7% and the precision values ranged from 1.4 to 8.1% for intra-day precision and from 3.1 to 6.4% for the inter-day values.

Carbamates↗
PubMed2001

[A "happy world"].

Explore the source record for details and available documents.

Drug Utilization↗
PubMed2001

The use of evidence in pharmacovigilance. Case reports as the reference source for drug withdrawals.

OBJECTIVE: Withdrawal of a drug from the market for safety reasons is a serious and sometimes complex decision. The scientific evidence supporting drug withdrawals in the past years is critically appraised. METHODS: With data provided by the Spanish Medicines Agency, all drugs withdrawn from the Spanish market for safety reasons from January 1990 to December 1999 were identified. The adverse drug reactions (ADRs) were classified by the year of withdrawal, by the organ/system affected and by the alleged type of reaction (Rawlins and Thompson classification). A systematic review of the literature was performed. RESULTS: A total of 22 drugs were withdrawn from the market due to safety reasons. In 18 of 22 cases (82%), the evidence supporting the drug withdrawal came from individual case reports, cases series or the combination of data provided by randomised clinical trials and case reports. Hepatic (eight cases) and cardiac (five cases) reactions accounted for 59% (13 of 22) of the total withdrawals. In 10 of 22 (45%) cases, drug withdrawal was clearly due to type-B reactions. Only four withdrawals were based on evidence from observational studies including a comparison group. CONCLUSION: Case reports are the main source of information used to withdraw a drug from the market for safety reasons. It is necessary to improve the quality of evidence supporting the withdrawal process of drugs linked to unexpected and severe ADRs. The use of large databases to perform cohort or nested case-control analyses is the most efficient and reliable method to study type-A class effect ADRs. The implementation of such databases in different countries could increase the quality of the information on ADRs by allowing researchers to conduct efficiently these type of studies.

Adverse Drug Reaction Reporting Systems↗
PubMed2000

Dose-finding study of once-daily indinavir/ritonavir plus zidovudine and lamivudine in HIV-infected patients.

BACKGROUND: Strategies for treatment of HIV need to be considered in terms of combining potency, safety, and convenience of dosage. However, regimens including once-daily protease inhibitors are not yet available. We have performed a pilot study to determine an indinavir/ritonavir (IND/RTV) regimen for once-daily dosing, by monitoring plasma levels. METHODS: Antiretroviral-naive HIV-infected adults were eligible. Therapy was zidovudine/lamivudine 1 pill twice daily plus IND/RIT (liquid formulation) 800/100 mg twice daily with food. At 4-week intervals, plasma levels were measured and dosage of IND/RIT switched to 1000/100 mg daily and then 800/200 mg daily. If 12-hour minimum concentrations (Cmin12h) of IND were too low (<0.1 microg/ml) with IND/RIT 1000/100 mg once daily in the first half of the patients, it was planned to switch directly to 800/200 mg once daily in the other half. RESULTS: In all, 27 patients were recruited. Mean baseline CD4+ lymphocyte count was 107 x 106/L (range, 4-623 x 106/L). Eleven patients (40%) discontinued the study medication within the first 4 weeks due to clinical progression (n = 3) or grade 1-2 RTV related side effects (n = 8). Nine patients (group A) switched from 800/100 mg twice daily to 1000/100 mg once daily and then to 800/200 mg once daily. Seven patients (group B) switched directly to 800/200 mg once daily. At week 32, viral load was <5 copies/ml in 15 of 16 patients (94%). RTV levels were always <2.1 microg/ml. The mean and 95% confidence interval for IND Cmin and Cmax in microg/ml was: using IND/RTV 800/100 mg twice daily (n = 16) 1.4 (0.5-2.3) and 6.7 (4.4-9.1), respectively; using IND/RTV 1000/100 mg once daily (n = 9) 0.18 (0-0.41) and 8.6 (3.3-14), respectively; and using 800/200 mg once daily (n = 16) 0.38 (0-0.9), and 7.5 (0.8-14.8). For all 16 patients who received IND/RTV 800/100 mg twice daily, the Cmin value for IND was >/=0.1 microg/ml. Conversely, IND Cmin was <0.1 microg/ml in 4 of 9 receiving 1000/100 mg once daily but in only 1 of 16 receiving 800/200 mg once daily. CONCLUSION: Once-daily regimen of IND/RIT is feasible and deserves further evaluation in larger randomized trials. Liquid formulation of RIT was not well tolerated by our antiretroviral-naive patients despite lower than suggested doses.

Adult↗
PubMed2000

Determination of stavudine in human plasma and urine by high-performance liquid chromatography using a reduced sample volume.

Sensitive high-performance liquid chromatographic assays have been developed for the quantification of stavudine (2',3'-didehydro-3'-deoxythymidine, d4T) in human plasma and urine. The methods are linear over the concentration ranges 0.025-25 and 2-150 microg/ml in plasma and urine, respectively. An aliquot of 200 microl of plasma was extracted with solid-phase extraction using Oasis cartridges, while urine samples were simply diluted 1/100 with HPLC water. The analytical column, mobile phase, instrumentation and chromatographic conditions are the same for both methods. The methods have been validated separately, and stability tests under various conditions have been performed. The detection limit is 12 ng/ml in plasma for a sample size of 200 microl. The bioanalytical assay has been used in a pharmacokinetic study of pregnant women and their newborns.

Anti-HIV Agents↗
PubMed2000

[Comparative analysis of articles published by Spanish authors (1993-1997) in biomedical journals with high impact factor].

BACKGROUND: To identify the Spanish scientific production amongst different areas of clinical knowledge, and to compare it with those of five other European Union countries. METHOD: Review of MEDLINE data base, for the period 1993-1997. Search limited to four journals, selected, for 10 different medical specialties (Cardiology, Endocrinology, Infectious Diseases, Gastroenterology-Hepatology, Haematology, Nephrology, Pneumology, Neurology, Oncology, Rheumatology). Articles published by authors from Germany, France, Italy, The Netherlands, Sweden and Spain. Journals included in the Internal Medicine subject classification were independently analysed. Data were also related with several econometric indexes. RESULTS: A total of 1,763 original articles published by Spanish authors were identified in the journal's sample over the analysed period (2.08 articles per 100 all published articles). Spain contributes to the total achieved by the six European countries analysed with 9.07 articles per 100 published articles. Gastroenterology-Hepatology was the medical specially which has more articles published by Spanish authors (total: 338 articles; 4.15 articles/100 published articles); and Oncology the one with less articles published (1.26 articles/100 published articles). The mean IF value per journal by article is highest for Gastroenterology-Hepatology (4.86 FI/article) and lowest for Pneumology (2.42 FI/article). Spain is the last amongst all six European countries analyzed in Endocrinology, Oncology and Haematology, and second to last in all others except for Gastroenterology-Hepatology (4th place). Mean cost for each article produced by Spanish authors in the analyzed sample was 0.49 US $ according the health expenditures per capita, and 0.07 US $ according the R+D expenditures per capita. Data from the independent analysis of Internal Medicine journals also showed that Gastroenterology and Hepatology is the subspecialty with a higher number of papers published in those journals. CONCLUSIONS: All efforts devoted to improve the quality of Spanish biomedical research, specially in clinical research, had produced positive, but uneven, results, measured by the number and impact factor of original articles published in top ranked biomedical journals. The overall distribution of high impact factor scientific production by specialties is poor when compared to the European Union countries included in the analysis. Those results showed several improvement opportunities. Besides increasing the overall budget for R+D, its is likely that the time has come for backing the highest quality Spanish biomedical research, the one that offers greater and better chances for achieving scientifically valid results, and is published in high impact factor biomedical journals.

Bibliometrics↗
PubMed2000

[Vancomycin and teicoplanin use as antibiotic prophylaxis in cardiac surgery: pharmacoeconomic study].

BACKGROUND: To assess the economical impact of vancomycin use versus teicoplanin use as antibiotic prophylaxis for patients undergoing cardiac surgery for valve replacement (VR) and coronary artery by-pass (CABS) procedures. PATIENTS AND METHODS: This is an ancillary cost minimization analysis of a double blinded, parallel groups, randomised clinical trial (RCT), with the main objective of comparing the safety and efficacy of these antibiotics. 500 patients were included in the study; 267 in the CABS group and 233 in the VR group. The CABS patients received 1 g vancomicin or 400 mg teicoplanin, plus 150 mg netilmicin. The VR group received a second dose of each drug after extracorporeal circulation. In order to calculate the costs we considered the direct cost of the drug, the i.v. mix and the administration costs, together with personnel and structure costs. We considered two different situations: the administration of drugs within the surgical room theatre and in the medical ward. RESULTS: The demographic data of both groups were comparable. The frequency of severe adverse drug reactions (ADR) were similar (0.4%) in both groups, as well as the post-operative infection rates (8.6%). Differences were seen in the frequencies of low severity ADRs: 20.4% in the vancomycin group and 1.6% in the teicoplanin group. When the antibiotics were administered in the surgical room, among CABS patients the costs were 8,265 pts. for the teicoplanin group and 12,005 pts. for the vancomycin group; while among VR patients, costs were respectively 11,661 pts. and 14,528 pts. Administration costs of teicoplanin and vancomycin within a medical ward setting, however, the costs were 6,740 pts. and 2,809 pts. for CABS patients, and 5,308 pts. and 10,140 pts. for VR patients, respectively. CONCLUSIONS: The costs of antibiotic prophylaxis among cardiac surgery patients heavily depends on the setting and circumstances of drug administration. The minimization cost analysis indicates that teicoplanin is the most cost-effective option if the drug is administered within the surgical area, while vancomycin is the less costly option when administered within the medical ward. However, if the second option is to be chosen, it is necessary to assure the right plasmatic drug levels of the antibiotic at the beginning of the surgical procedure.

Aged↗
PubMed2000

[Analysis of the cost-effectiveness relationship in the empirical treatment in patients with infections of the lower respiratory tract acquired in the community].

BACKGROUND: Cost of treatment of community-acquired infections in Spain is an important factor in overall health expenditures. The aim of this study was to assess the direct health costs related with the treatment of patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) due to infection, using different antibiotic options, and to identify main cost drivers. METHODS: A basic decision analysis model was developed, including probabilities estimation derived from the literature review, supplemented when needed by the opinion of a panel of 8 Spanish physicians (Delphi technique). Four groups of antibiotics were included (macrolides, beta-lactam, fluoroquinolones and cephalosporins) in two different groups: patients with CAP without hospital admission criteria and patients with AECB due to respiratory infection. The analytic horizon and the perspective used were those of the Spanish National Health Service. Direct cost were assessed (drugs, outpatient visits, hospital admissions, diagnostic tests). Indirect cost were not included in the model. Final costs uses as main outcome measure the average cost per patient treated. All results were calculated following a fold-back technique. Sensitivity analysis were included allowing for variations in several clinically relevant parameters. RESULTS: 1. Patients with CAP: Hospital admissions, directly related to the effectiveness rate of initial empirical antibiotic therapy, were the main cost driver (50%-70%). Acquisition costs of initial antibiotic therapy only account for 2%-13% of total costs. 2. Patients with AECB: Outpatient visits are the main cost driver for these group of patients (49% of total costs). Hospital admission costs are also an important cost driver (40%-51% of total costs). Acquisition costs of initial antibiotic therapy account for 4%-28% of total costs. Clinical effectiveness of first antibiotic option is the main variable regarding the cost-effectiveness rate. CONCLUSION: The model here presented showed that acquisition costs of first empirical antibiotic therapy are only a small proportion of total costs related with the management of community acquired lower respiratory tract infections in Spain. The clinical effectiveness rate of the first antibiotic used is the main variable which determines the final average cost per patient cured. For patients with lower respiratory tract infections the therapeutic option with a better cost-effectiveness ratio must be chosen, in order to minimize the risk of therapeutic failure after first line therapy, and should not be selected only by its lower acquisition costs.

Anti-Bacterial Agents↗