ABSTRACT
Capecitabine is an important oral fluoropyrimidine anticancer drug. The purpose of this study was to overcome limitations of previously reported methods and propose an optimized and widely available tool for analysis of capecitabine in human plasma. The simplification of the liquid-liquid extraction procedure involved elimination of unnecessary addition of phosphoric acid and reduction of the extraction solvent volume. The use of voriconazole as the internal standard, combined with gradient elution and on-line wavelength switching, assured very high within- and between-run precision of results (relative standard deviation < 7.1% for lower limit of quantification) and enabled the reduction of the total chromatographic run time to 8 min. The calibration curve was linear within the range of 0.05-10.00 microg/mL and the method selectivity was confirmed in the presence of capecitabine metabolites. All validation parameters met the acceptance criteria set by international regulatory guidances, which proves that the method leads to reliable results. The method may be applied in human pharmacokinetic studies, for the regulatory purposes and therapeutic drug monitoring.
Subject(s)
Antimetabolites, Antineoplastic/blood , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Antimetabolites, Antineoplastic/pharmacokinetics , Biotransformation , Calibration , Capecitabine , Chromatography, High Pressure Liquid , Deoxycytidine/blood , Deoxycytidine/pharmacokinetics , Fluorouracil/blood , Fluorouracil/pharmacokinetics , Humans , Liquid-Liquid Extraction , Online Systems , Prodrugs , Quality Control , Reference Standards , Reproducibility of Results , Spectrophotometry, UltravioletABSTRACT
The aim of the study was to investigate the bioequivalence of a generic product of 8 mg film-coated tablets (test) to the branded product (reference) at the same strength in order to apply for regulatory approval. The secondary objective of the study was to compare the tolerability of both products. A double blinded, randomized, cross-over, 2-period, comparative study was conducted in healthy Caucasian volunteers under fasting conditions. A single oral dose administration of the test or reference product was followed by a 7-day wash-out period. The ondansetron concentration was determined using a validated high performance liquid chromatography with a UV detection method. The 90% confidence interval of the point estimate (test over reference products) for C(max) and AUC(0-t) fell within the 80.00-125.00% acceptance range. The results of the study indicate that the film-coated tablets of Ondatron 8 mg manufactured by Tarchominskie Zaklady Farmaceutyczne Polfa S.A. (test product) are bioequivalent to those of Zofran manufactured by GlaxoSmithKline Export Ltd (reference product). Both products were well tolerated.
Subject(s)
Ondansetron/pharmacokinetics , Adolescent , Adult , Cross-Over Studies , Double-Blind Method , Female , Healthy Volunteers , Humans , Male , Middle Aged , Ondansetron/adverse effects , Tablets , Therapeutic EquivalencyABSTRACT
Acute hazard classification based on selected microbiotests was proposed to assess and compare the toxicity of rivers including surface-water, sediment and soil from floodplains. No direct relationship between the classification of pollution for surface-water based on physical-chemical parameters and proposed acute hazard classification based on organisms' sensitivity was observed. The quality of water according to hazard classification was better than in the mandatory classification of pollution, with the domination of Class II (slight acute hazard). The samples of sediment and soil were more toxic and represented Class II or Class III (acute hazard). The results indicated a need to complete the mandatory monitoring of surface-water in rivers with biological monitoring with toxicity assessment of rivers including water, sediment and soil from floodplains based on acute hazard classification. This integral approach enables a complete evaluation of the toxicity of aquatic life together with an estimation of negative changes in river systems.
Subject(s)
Environmental Monitoring/methods , Rivers/chemistry , Water Pollutants, Chemical/toxicity , Aliivibrio fischeri/drug effects , Animals , Aquatic Organisms/drug effects , Crustacea/drug effects , Food Chain , Geologic Sediments/chemistry , Hazardous Substances/toxicity , Microalgae/drug effects , Plants/drug effects , Rotifera/drug effects , Soil Pollutants/toxicityABSTRACT
OBJECTIVE: To estimate knowledge, experience, and attitudes towards the use of electroconvulsive treatment in minors (patients < 18 years of age), among child and adolescent psychiatrists and psychologists. METHOD: 1,600 questionnaires were mailed to a group of child and adolescent psychiatrists and psychologists. RESULT: There were 625 (39%) respondents. 329 (53.8%) of the respondents stated that they possessed minimal knowledge about the use of ECT in children and adolescents. Lack of confidence in providing a second opinion was common and reported by 75%. Compared with those with minimal knowledge, respondents with advanced knowledge reported a higher perception of safety and efficacy. The majority (70%) of the respondents regarded ECT as a treatment of last resort. CONCLUSION: Many child and adolescent psychiatrists and psychologists have very little knowledge, training, or experience in this treatment. They seem to be ill equipped to appropriately consider or advise patients and families about ECT. Clinical and research implications of these findings are discussed.
