Ucinek a farmakokinetika nizkodavkovaneho metotrexatu v lecbe psoriazy.

Two clinical studies with low-dose methotrexate (LDMTX) in the therapy of psoriasis were performed to answer if the relationship between the pharmacokinetics (PK) and pharmacodynamics (PD) exists and if it is possible to use results for the dose optimization in clinical practice. 11 patients were treated with 15 mg MTX and 7 patients with 7,5 mg MTX once a week. To perform a detailed evaluation of PK, plasma samples were drawn and urine was collected before and at the 13th week of the drug administration. The concentrations of MTX and its chief metabolite 7-OHMTX were determined by HPLC with UV detection. Maximum plasma concentration, time to reach a maximum plasma conc., the area under the plasma conc. time curve and renal clearance of MTX were measured and calculated. Similar PK was determined for 7-OHMTX. The data were used to correlate PK and PD. The efficacy of the therapy was evaluated by the PASI score. The score evaluates a clinical severity of psoriasis. At the end of the study the PASI score was calculated in percent of its initial value. MTX has the intracellular mechanism of action. Therefore, LDMTX efficacy and toxicity was evaluated in respect to MTX intracellular conc. in erythrocytes in steady state. The data were achieved by enzymatic spectrophotometry, evaluation of dihydrofolatereductase activity decrease in the presence of MTX. The study showed at least 4-times higher interindividual variability of PK parameters if compared to intraindividual var.. However, the therapy with 7,5 mg MTX was not very successful because of the low efficacy. Otherwise, the administration of 15 mg MTX as a bolus led to adverse effects (headache or nausea). Therefore, the next study was performed with LDMTX 7,5 and 15 mg a week divided into three aliquots given at 12-hour intervals. The divided dose schedule seems to be more convenient.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Selected Risk Nutritional Factors for Chemotherapy-Induced Polyneuropathy

The present study seeks to identify the nutritional risk factors involved in the development of neuropathies induced by chemotherapeutic treatments. Unlike the gastrointestinal or hematological adverse effects of chemotherapy there is no protective treatment strategy for polyneuropathy. The aim of this study was to find possible deficiencies in nutritional factors, which can be used for supplementation in the future for prevention of chemotherapy-induced neuropathy development. We analyzed 70 patients undergoing paclitaxel chemotherapy and evaluated the risk factors involved in chemotherapy-induced peripheral neuropathy (CIPN). Several risk factors were considered in the development of CIPN, including deficiency of vitamin B1, B6, and D and fatty acids. The occurrence of CIPN complication in 60% cases was observed. We found significant differences in vitamin D and saturated fatty acid concentration. Vitamin D levels in the group without CIPN were estimated to be 38.2 (24.95, 47.63) nmol/L, whereas in the group with CIPN it was determined to be 25.6 (19.7, 32.55) nmol/L, p = 0.008. The level of total saturated fatty acids in the group without CIPN was of 32.613 Area % (31.322; 36.262), whereas in the group with CIPN it was of 34.209 Area % (32.86; 39.386), p = 0.01. The obtained results suggest a diet lower in saturated fatty acid content during chemotherapy. The most significant finding was that supplementation of vitamin D before chemotherapy could be an efficient neuroprotective in CIPN prophylaxis, as significantly lower levels 25OH derivative of vitamin D were observed in the CIPN group throughout the study period

Bioequivalence of a New Pediatric Paracetamol Oral Suspension Compared With a Marketed Formulation in Healthy Adults: A Randomized, Open-Label Study

ABSTRACT: Background: A new oral paracetamol formulation with the same paracetamol quantity (24 mg/mL) as a marketed formulation but with finer active ingredient particle size and lower amounts of maltitol (5.85 g/dose in the test formulation vs 7.25 g/dose in the reference formulation) and sorbitol (2.4 g/dose vs 2.83 g/dose) was developed. Objective: Establish the bioequivalence of the new pediatric formulation (test treatment) compared with the marketed formulation (reference treatment). Methods: This Phase I, open-label trial assigned healthy adult volunteers to a single 42-mL (1 g para-cetamol) dose of test or reference treatment. Participants received both treatments in a randomized order separated by a 72-hour washout period. The primary endpoints were AUC0–tlast (AUC vs time curve from time 0 to last measurable sampling timepoint), Cmax, and tmax. Safety assessments included adverse event, clinical laboratory, and physical examination data. Results: Thirty-five participants were randomized and treated. The study population was 42.9% women (57.1% men) with a median age of 30 years; most participants were non-Hispanic White. Mean Cmax values were comparable between test and reference products, with a median tmax of 1.00 hour for both. The test/reference ratios (%) (90% CI) for AUC0–tlast and Cmax were 98.69% (96.46, 100.97) and 100.73% (95.63, 106.10), respectively. There were no adverse events or deaths. Conclusions: The new paracetamol formulation is bioequivalent to the marketed formulation