Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) patients, some individuals develop resistance due to impaired bioavailability. It has been previously demonstrated that the haplotypes for ATP-binding cassette subfamily B member 1 (ABCB1)with c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms markedly affect the secondary structure of ABCB1 mRNA and its activity. These modifications may affect efflux transporter activity and response to treatment with IM. The aim of the present study was to investigate the influence of ABCB1 haplotypes on P-glycoprotein (P-gp) activity, IM plasma levels and IM response. In total, 28 chronic-phase CML patients treated with a standard dose of IM (400 mg/day) were studied. The patients were selected according to the haplotypes of ABCB1, with c.1236C>T, c.3435C>T and c.2677G>T polymorphisms, and were classified into two groups based on the presence of the mutated allele in each genotype for the three ABCB1 polymorphisms. In addition, expression of P-gp and breakpoint cluster region-abelson 1 (BCR-ABL1), ABCB1 and solute carrier family 22 member 1 (SLC22A1) mRNA were evaluated. The P-gp activity in the wild-type group was found to be higher than that in the mutated group (59.1 vs. 38.3%; P=0.001). Furthermore, the patients who did not achieve major molecular response (MMR) showed a higher rate of efflux mediated by P-gp when compared with individuals who achieved MMR (64.7 vs. 45.7%; P=0.001). All patients without MMR demonstrated effluxes of >60%. In addition, patients without MMR exhibited lower plasma concentrations of IM compared with those with MMR (0.51 vs. 1.42 μg/ml; P=0.001). Higher levels of SLC22A1 mRNA were observed in patients who achieved MMR and complete molecular response (P<0.05). In conclusion, the ABCB1 1236CT/3435CT/2677GT and 1236TT/3435TT/2677TT haplotypes are associated with reduced P-gp activity and MMR in chronic-phase CML patients treated with a standard dose of IM.

Levetiracetam (LEV) is an antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes. The use of this drug has been increasing in clinical practice and intra- or -interindividual variability has been exhibited for special population. For this reason, bioanalytical methods are required for drug monitoring in biological matrices. So this work presents a dispersive liquid-liquid microextraction method followed by gas chromatography-mass spectrometry (DLLME-GC-MS) for LEV quantification in human plasma. However, due to the matrix complexity a previous purification step is required. Unlike other pretreatment techniques presented in the literature, for the first time, a procedure employing ultrafiltration tubes Amicon® (10 kDa porous size) without organic solvent consumption was developed. GC-MS analyses were carried out using a linear temperature program, capillary fused silica column, and helium as the carrier gas. DLLME optimized parameters were type and volume of extraction and dispersing solvents, salt addition, and vortex agitation time. Under chosen parameters (extraction solvent: chloroform, 130 μL; dispersing solvent: isopropyl alcohol, 400 μL; no salt addition and no vortex agitation time), the method was completely validated and all parameters were in agreement with the literature recommendations. LEV was quantified in patient's plasma sample using less than 550 μL of organic solvent.

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RESUMOOs antiinflamatórios não-esteróides (AINE's), integram o grupo dos fármacos mais comumente prescritos mundialmente e estão entre os mais utilizados nas práticas de automedicação. Possuem propriedades antiinflamatórias, analgésicas e antipiréticas. Autores afirmam que é importante evitar prescrever em gota, quando se deseja uma dose exata, pois o volume de uma gota varia com a densidade e viscosidade do líquido, e com o orifício do gotejador e o ângulo no qual se goteja. Como os gotejadores utilizados na indústria não são padronizados, este trabalho tem como objetivo avaliar as diferenças de concentração, em miligramas/gota, de 10 diferentes marcas de medicamentos contendo diclofenaco resinato na apresentação de gotas orais (15mg/mL), de acordo com suas bulas e com o número de gotas por mL para cada gotejador, comparando com as doses indicadas pela literatura.Palavras-chave: diclofenaco resinato; gotejadores; dose de medicamento. ABSTRACTNon steroidal anti-inflammatory (NSAID) integrates the group of drugs more commonly prescribed world-wide and also are used in the practical of self-medication. They possess anti-inflammatory, analgesic and antipyretic properties. Authors affirm that it is important to prevent to prescribe drops, when desire an accurate dose, because the volume of a drop varies with the density and viscosity of the liquid, and with the orifice of the bottle dropper and the angle in which it drips. As the bottle droppers used in the industry are not standardized, this work has as objective to evaluate the concentration differences, in milligrams/drop, of 10 different medicine marks of diclofenac resinate in the presentation of oral drops (15mg/mL), in accordance with its drug package inserts and with the number of drops for mL for each bottle dropper, comparing with the doses indicated in the literature.